Inflammation (INFLAMMATION)

Publications in this journal

• Article: Destruction of Salivary and Lacrimal Glands by Th1-Polarized Reaction in a Model of Secondary Sjögren’s Syndrome in Lupus-Prone Female NZB × NZWF1 Mice

  Toshiharu Hayashi, Natsumi Shimoyama, Takuya Mizuno
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  ABSTRACT: T helper (Th)1/Th2 balance determines the direction of some kinds of autoimmune diseases. The involvement of acini areas by CD4+ helper T(Th) cell subset in submandibular and lacrimal glands are largely unknown in secondary Sjögren’s syndrome (sSjS) with systemic lupus erythematosus (SLE). Submandibular and lacrimal glands were examined immunopathologically in lupus-prone female NZB × NZW(B/W)F1 mice, model for human sSjS with SLE. Dacryoadenitis and sialoadenitis with renal failure developed with age. Infiltration of lymphoid cells (lymphocytes and plasma cells) expanded from the periductal areas in striated ducts to the acini, and the isolated foci in the acini were observed in those organs. The destruction of duct and acini epithelium, including the myoepithelium, was induced by interferon (IFN)-γ+ and IgG2a+ lymphoid cells, but not by interleukin(IL)-4+, IL-5+, IL-13+, and IgG1+ lymphoid cells. Compared with IL-5 and IL-13, high values of IFN-γ were produced systemically at various ages. Also local expression of IFN-γ mRNA was higher than that of IL-4 mRNA. The result suggests that the acini destruction in submandibular and lacrimal glands may be induced by systemic and local Th1 cell dominant reactions in lupus-prone B/WF1 mice with sSjS. KEY WORDSsecondary Sjögren’s syndrome–acini–lupus–Th1–Th2–female–B/WF1 mice
  Inflammation 04/2012; 35(2):638-646.
• Article: Comparison of Pulmonary Inflammatory and Antioxidant Responses to Intranasal Live and Heat-Killed Streptococcus pneumoniae in Mice

  Miroslava Dominis-Kramari, Martina Bosnar, Željko Kelneri, Ines Glojnari, Snježana Čuži, Michael J. Parnham, Vesna Erakovi Haber
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  ABSTRACT: Inflammatory and antioxidant responses, in male C57Bl6J mice, to single intranasal inoculations with live or heat-killed Streptococcus pneumoniae were studied in order to tease out differences in responses. Heat-killed bacteria elicited weak lung neutrophil infiltration and raised concentrations (peak 6–8h), in serum or lung tissue, of CXCL1 and 2, tumor necrosis factor alpha (TNFα), interleukin-6 (IL-6), and granulocyte-macrophage-colony stimulating factor, with later increases in CCL2 and IL-1β. Live bacteria induced profound pulmonary neutrophil infiltration and acute chemokine/cytokine elevations. After 72–96h, live S. pneumoniae induced a delayed rise in chemokines CXCL2 and CCL2, preceded by increases in TNFα, IL-1β, and IL-6 and mononuclear infiltration of lungs. With both live and heat-killed bacteria, alveolar epithelial type II cells and alveolar macrophages were the main sources of TNFα and IL-1β. Only live bacteria caused an acute decrease in lung glutathione peroxidase, an increase in superoxide dismutase, and a sustained increase in serum amyloid protein A. Acute innate immune responses to live and heat-killed S. pneumoniae are similar. In response to live bacteria, inflammation is greater, accompanied by changes in antioxidant enzymes and has an additional, later mononuclear component. KEY WORDS S. pneumoniae infection–murine lung inflammation–pro-inflammatory cytokines–antioxidant enzymes
  Inflammation 04/2012; 34(5):471-486.
• Article: Changes in Peripheral CD4+CD25high Regulatory T Cells in the Acute-on-Chronic Liver Failure Patients with Plasma Exchange Treatment

  Wei-lin Mao, Yu-Feng Lou, Bo Ye, Sha Lin, Yue-mei Chen, Yu Chen
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  ABSTRACT: The prevalence of CD4+CD25high regulatory T cells (Tregs) in patients with acute-on-chronic liver failure (AoCLF) who received plasma exchange (PE) and/or medical treatment was investigated. One hundred five patients with AoCLF in two groups (PE plus routine-care, n = 48 and routine-care, n = 57) were enrolled in our study. In the PE group, there were 27 survivors (27/48) while, in the routine-care group, there were 18 survivors (18/57), both after 30days treatment. Twenty-three healthy donors were used as the control group. Tregs were determined by flow cytometry serially. In the survivors, Tregs frequency were lower compared with the normal controls on admission and showed an up and down tendency; moreover, this frequency turned to the level as that in healthy subjects and was faster in the PE compared with the medical group while, among the nonsurvivors, Tregs stayed at a high level throughout the examination period. Importantly, an increased quantity of Tregs was associated with high mortality and reduced survival time of AoCLF patients. These data suggest that Tregs play a role in determining the patient’s fate toward either a favorable or unfavorable clinical course of disease, and PE may represent a reliable hepatic support device for AoCLF. KEY WORDSregulatory T cells–acute-on-chronic liver failure–plasma exchange
  Inflammation 04/2012; 35(2):436-444.
• Article: Activatory Properties of Lysophosphatidic Acid on Human THP-1 Cells

  F. D’Aquilio, M. Procaccini, V. Izzi, V. Chiurchiu’, V. Giambra, F. Carotenuto, P. Di Nardo, P. M. Baldini
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  ABSTRACT: Excessive leukocyte proliferation and proinflammatory mediators release represent common phenomena in several chronic inflammatory diseases. Multiple evidences identify lysophosphatidic acid (LPA), a small lipid endowed with pleiotropic activities, as an important modulator of both proliferation and activation of different cell types involved in several inflammation-associated pathologies. However, its possible role on monocyte proinflammatory activation is not fully understood yet. Aim of the present study was to investigate LPA effects on THP-1 cells in terms of proliferation, reactive oxygen intermediates (ROI) production and release of arachidonic acid-derived inflammatory mediators. Actually, LPA significantly increased both DNA synthesis and ROI production as well as prostaglandin E2 release and the upregulation of LPA3 receptor expression. These findings identified LPA as both a growth factor and a triggering mediator of proinflammatory response in THP-1 cells.
  Inflammation 04/2012; 29(4):129-140.
• Article: The Effect of A2A Adenosine Receptor Activation on C-C Chemokine Receptor 7 Expression in Human THP1 Macrophages During Inflammation

  Adrienne J. Williams, Bruce N. Cronstein
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  ABSTRACT: C-C chemokine receptor 7 (CCR7) and its chemoattractant agonist CCL21 promote cell migration and expression of pro-inflammatory proteins in an atherogenic environment. Since A2A adenosine receptor activation reduces migration and inflammatory effects, we examined its effect on CCR7 expression and migration. CCR7 protein expression decreased by about a third in macrophages treated with A2A receptor agonist CGS 21680 (p = 0.028, n = 7) and was reversed with antagonist, although mRNA levels increased twofold (p = 0.001, n = 3). Furthermore, macrophages treated with CGS 21680 showed a significant decrease in migration (p = 0.0311, n = 7). These results suggest that A2A adenosine receptor activation not only modulates CCR7 expression in both normal and inflammatory environments but also regulates macrophage migration to CCR7-specific chemoattractants. KEY WORDSA2A adenosine receptor–macrophage–chemokine receptor migration
  Inflammation 04/2012; 35(2):614-622.
• Article: Evaluation of the Anti-inflammatory and Anti-tumor Effect of Ipomoea obscura (L) and Its Mode of Action Through the Inhibition of Pro Inflammatory Cytokines, Nitric Oxide and COX-2

  T. P. Hamsa, Girija Kuttan
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  ABSTRACT: Ipomoea obscura (L) is a widely used medicinal plant. In this study, we investigated its anti-inflammatory and anti-tumor effect using in vitro and in vivo models. Methanolic extract of I. obsucra (10mg/kgb.wt) was given interaperitoneally before inducing inflammation (both acute and chronic) and tumor to mice. I. obscura produced significant inhibition of 55.6%, 42%, and 65% in the paw edema of animals induced by carrageenan, dextran, and formalin respectively. The extract was also a potent inhibitor of lipopolysaccharide (LPS)-induced NO, CRP, and proinflammatory cytokine production via gene expression in peritoneal macrophages. TNF-α production by macrophage culture treated with LPS was found to be significantly inhibited by I. obscura. The extract was 100% toxic at a concentration of 500µg/mL for both Dalton’s lymphoma ascites (DLA) and Ehrlich ascites carcinoma (EAC) cells. The extract was also found to inhibit tumor cell proliferation in a dose and time-dependent manner. It could also inhibit solid tumor development in mice induced with DLA cells and increased life span of mice bearing EAC tumor to 83% and 53.8%, respectively. This anti-inflammatory effect of the extract is assumed to result mainly from the inhibition of some key enzymes and mediators involved in the inflammation and/or cell signaling pathways such as iNOS, COX-2, and proinflammatory cytokines. This anti-inflammatory property might be the reason for its anti-tumor effects. KEY WORDSanti-inflammatory agent–anti-tumor agent– Ipomoea obscura –lipopolysaccharide–paw edema–proinflammatory cytokine
  Inflammation 04/2012; 34(3):171-183.
• Article: Prolonged Administration Enhances the Renoprotective Effect of Pentoxifylline via Anti-Inflammatory Activity in Streptozotocin-Induced Diabetic Nephropathy

  Kum Hyun Han, Sang Youb Han, Han Seong Kim, Young Sun Kang, Dae Ryong Cha
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  ABSTRACT: The beneficial effects of pentoxifylline (PTX), which has an anti-inflammatory and renoprotective effect in diabetic nephropathy, are not completely understood. This study investigates whether prolonged administration of PTX (40mg/kg, per oral) is effective in streptozotocin-induced diabetic nephropathy. The amount of urinary protein was higher in the diabetic rats than in the control rats. The amount remained unchanged after 4weeks and decreased after 8weeks of PTX treatment. Accumulation of monocyte chemoattractant peptide-1 (MCP-1) and mouse monoclonal anti-monocyte/macrophage antibody (ED-1) positive cells was higher in untreated diabetic rats than in the control rats. PTX administration ameliorated the urinary MCP-1 excretion and interstitial infiltration of ED-1 positive cells at 4weeks. Further, in diabetic rats, administration of PTX for 4weeks inhibited the renal inflammatory reaction, and when administration for 8weeks, it prevented proteinuria. These findings support the hypothesis that prolonged administration enhances the protective effects of PTX. KEY WORDSdiabetic nephropathy-inflammation-pentoxifylline
  Inflammation 04/2012; 33(3):137-143.
• Article: Activation of PPAR-γ by Carbon Monoxide from CORM-2 Leads to the Inhibition of iNOS but not COX-2 Expression in LPS-Stimulated Macrophages

  Konstantin Tsoyi, Yu Mi Ha, Young Min Kim, Young Soo Lee, Hyo Jung Kim, Hye Jung Kim, Han Geuk Seo, Jae Heun Lee, Ki Churl Chang
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  ABSTRACT: The effect of CO on the expression of iNOS and COX-2 was investigated by using a CO-releasing molecule (CORM)-2 in LPS-activated RAW 264.7 cells in vitro. Interestingly, CORM-2 significantly inhibited iNOS (NO) but not COX-2 (PGE2) expression. PPAR-γ activators such as troglitazone, GW1929, and 15-deoxy-Δ12, 14- prostaglandin J2 showed preferential inhibitory effect on iNOS over COX-2 expression in LPS-activated macrophages. The same effect was shown in lung tissues (iNOS, COX-2) and serum (NO, PGE2) when administered of CORM-2 in LPS-induced septic mice, indicating that CO derived from CORM-2 differentially regulates iNOS and COX-2 through PPAR-γ activation under inflammation state.
  Inflammation 04/2012; 32(6):364-371.
• Article: Topical Azithromycin and Clarithromycin Inhibit Acute and Chronic Skin Inflammation in Sensitized Mice, with Apparent Selectivity for Th2-Mediated Processes in Delayed-Type Hypersensitivity

  Vanesa Ivetić Tkalčević, Snježana Čužić, Miroslava Dominis Kramarić, Michael J. Parnham, Vesna Eraković Haber
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  ABSTRACT: Macrolide antibiotics inhibit the secretion of Th1 cytokines while their effects on the release of Th2 cytokines are variable. We investigated molecular and cellular markers of Th1- and Th2-mediated inflammatory mechanisms and the anti-inflammatory activity of azithromycin and clarithromycin in phorbol 12-myristate 13-acetate (PMA) and oxazolone (OXA)-induced skin inflammation. Dexamethasone (50μg/ear), azithromycin, and clarithromycin (500μg/ear) reduced TNF-α and interleukin (IL)-1β concentration in ear tissue by inhibiting inflammatory cell accumulation in PMA-induced inflammation. In OXA-induced early delayed-type hypersensitivity (DTH), the macrolides (2mg/ear) and dexamethasone (25μg/ear) reduced ear tissue inflammatory cell infiltration and secretion of IL-4 while clarithromycin also decreased IFN-γ concentration. Macrolides showed better activity when administered after the challenge. In OXA-induced chronic DTH, azithromycin (1mg/ear) reduced the number of ear tissue mast cells and decreased the concentration of IL-4 in ear tissue and of immunoglobulin (Ig)E in serum. Clarithromycin (1mg/ear) reduced serum IgE concentration, possibly by a mechanism independent of IL-4, while both macrolides attenuated mast cell degranulation. In conclusion, azithromycin and clarithromycin attenuate pro-inflammatory cytokine production and leukocyte infiltration during innate immune reactions, while selectively affecting Th2 rather than Th1 immunity in DTH reactions. KEY WORDSmacrolide anti-inflammatory activity–oxazolone–PMA–skin inflammation–Th2 cytokines
  Inflammation 04/2012; 35(1):192-205.
• Article: Aspirin Inhibits MMP-2 and MMP-9 Expression and Activity Through PPARα/γ and TIMP-1-Mediated Mechanisms in Cultured Mouse Celiac Macrophages

  Yao Yiqin, Xie Meilin, Xue Jie, Zhang Keping
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  ABSTRACT: Aspirin is an anti-inflammatory drug, and has been widely used for the prevention of cardio-cerebrovascular events. Matrix metalloproteinase (MMP)-2 and MMP-9 can degrade the extracellular matrix and may be critical for the development and disruption of atherosclerotic plaques, while tissue inhibitor of metalloproteinase (TIMP)-1 may inhibit the degradation of extracellular matrix. The purpose of present study was to investigate the inhibitory effects of aspirin on MMP-2 and MMP-9 expression and activity in cultured mouse celiac macrophages, and to determine the possible mechanisms. The results showed that MMP-2/9 mRNA expression and release were significantly decreased after cultured mouse celiac macrophages were treated with aspirin 12.5–50μg/ml for 24h, while the TIMP-1 mRNA expression and release, and peroxisome proliferator-activated receptor (PPAR) α/γ mRNA expression were increased after the same treatment. Moreover the aspirin-induced down-regulation of MMP-2/9 mRNA expression and reduction of MMP-9 release were notably alleviated after pretreatment with specific inhibitors of PPARα/γ. These results suggested that aspirin could inhibit the expression and release of MMP-2/9 by up-regulation of PPARα/γ gene expression, and also inhibit the activity of MMP-2/9 by induction of TIMP-1 expression, which might be good for the stabilization of atherosclerotic plaques and the prevention of cardio-cerebrovascular events.
  Inflammation 04/2012; 32(4):233-241.
• Article: Synergistic effect of histamine and TNF-alpha on monocyte adhesion to vascular endothelial cells

  Chong Chen and Damir Khismatullin
  Inflammation 01/2012;
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  Available from: smu.edu.cn

  Article: Temperature pretreatment alters the polarization response of human neutrophils to the chemoattractant N-formyl-Met-Leu-Phe.

  Dongliang Zhao, Xiaojing Meng, Chunqing Cai, Chunhua Yuan, Fei Zou
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  ABSTRACT: Neutrophils present a polarized morphology upon stimulation of chemoattractants, which play a vital role in host-defense mechanisms. Many studies have been published on neutrophil polarization, in which three different temperatures pretreatment (4 degrees C, 25 degrees C and 37 degrees C) have been used. However, no study has investigated whether different temperature pretreatments affect neutrophil polarization. In the current study, we examined the effects of 4 degrees C, 25 degrees C and 37 degrees C pretreatment temperatures on short-term (1 or 3 min) chemoattractant-induced polarization. Human neutrophils were polarized upon the stimulation of N-formyl-Met-Leu-Phe (fMLP) after pretreated by different temperature. The morphological changes of the neutrophils were investigated under the microscopy. The F-actin polymerization was determined by immunological histological chemistry. There were more head-tail polarized cells (>50% of the cells) in the 25 degrees C and 37 degrees C pretreatment groups than in the 4 degrees C group (32.4%). The average lengths of the pseudopod were 3.2 +/- 1.1 microm (n = 17), 5.3 +/- 2.1 microm (n = 12) and 7.4 +/- 2.7 microm (n = 21) in the 4 degrees C, 25 degrees C and 37 degrees C pretreatment groups, respectively; the 4 degrees C and 37 degrees C pretreatment groups were statistically different (P < 0.05). Additionally, there was a statistically significant difference in the pseudopod extension rate among the three groups, as well as the Lamellipod percentage between the 4 degrees C group and the other two groups within 1 min of stimulation with fMLP. This study demonstrates that different temperature pretreatments affect neutrophil polarization upon short-term stimulation with fMLP.
  Inflammation 01/2009; 32(1):47-56.
• Article: Edematogenic activity of scorpion venoms from the Buthidae family and the role of platelet-activating factor and nitric oxide in paw edema induced by Tityus venoms.

  D N Severino, R L Pereira, I Knysak, D M Cândido, F H Kwasniewski
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  ABSTRACT: We compared the edematogenic activity of venoms of scorpions from the Buthidae family, Tityus bahiensis (Tbv), Tityus serrulatus (Tsv) and Rhopalurus rochai (Rrv). Three doses (20, 40 and 80 microg/kg sc) of each venom were administrated in hind paw of mice and edema was measured from 5 min to 24 h. Tbv and Tsv both induced edema of rapid onset (135% of increase at 15 min); Rrv induced only a mild edema (40% of increase). We then investigated the involvement of platelet-activating factor (PAF) and endogenous nitric oxide (NO) in Tbv and Tsv-induced paw edema. Pretreatment of mice with a PAF antagonist (WEB-2170) inhibited Tsv but not Tbv-induced edema. Pretreatment with a non selective inhibitor of NO-synthases (L: -NAME) inhibited or increased the edema depending on the dose and the time the edema was measured. In conclusion, the venoms from Tityus are stronger inducers of edema than the venom from the Rhopalurus scorpion. The venoms of Tityus species are similar in potency and time-course edema development. PAF is involved in the edema induced only by Tsv.
  Inflammation 01/2009; 32(1):57-64.
• Article: Alpha-lipoic acid improves acetic acid-induced gastric ulcer healing in rats.

  Berna Karakoyun, Meral Yüksel, Feriha Ercan, Can Erzik, Berrak C Yeğen
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  ABSTRACT: To evaluate the role of ALA treatment on the healing of acetic acid-induced gastric ulcer, rats were given ALA (35 mg/kg/day) or saline for 3 days before the induction of ulcer and the treatment was continued twice daily for 2 days (early) or 10 days (late) until they were decapitated. Gastric ulcer index, microscopic score, elevated DNA fragmentation and chemiluminescence levels of the saline-treated ulcer groups were all reduced by ALA treatment. Likewise, ALA treatment inhibited chemiluminescence levels in both early and late ulcer groups. Marked reduction in glutathione levels of the saline-treated early ulcer group was reversed by ALA treatment, while ALA treatment was effective in depressing gastric myeloperoxidase activity in the late ulcer group. In conclusion, ALA treatment shows protective role in the healing of acetic acid-induced gastric injury in rats via the suppression of neutrophil accumulation, preservation of endogenous glutathione, inhibition of reactive oxidant generation and apoptosis.
  Inflammation 01/2009; 32(1):37-46.
• Article: Effect of unfiltered coffee on carbon tetrachloride-induced liver injury in rats.

  Orhan Kursat Poyrazoglu, Ibrahim Halil Bahcecioglu, Huseyin Ataseven, Kerem Metin, Adile Ferda Dagli, Mehmet Yalniz, Bilal Ustundag
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  ABSTRACT: To assess the role of unfiltered coffee upon carbon tetrachloride (CCl(4)) induced hepatotoxicity in rats. All rats were randomly divided into control group, CCl(4)-treated, unfiltered coffee-treated and CCl(4)/unfiltered coffee-treated. Hepatic damage was induced by repeated intraperitoneal injections of CCl(4) every other day. Unfiltered coffee was given as drinking fluid for 8 days starting the day before CCl(4) administration. Liver enzymes, plasma and liver tissue malondialdehyde were analyzed. Histopathological evaluation of liver sections was performed. Serum aminotransferase level significantly increased in CCl(4)/unfiltered coffee-treated group compared to CCl(4)-treated group, as well as, lipid peroxidation products in the plasma and liver tissue. In addition, histopathological findings including inflammation and necrosis were significantly confirmed these findings. Unfiltered coffee potentiates acute liver injury in rats with CCl(4)-induced hepatotoxicity.
  Inflammation 01/2009; 31(6):408-13.
• Article: Local inflammation exacerbates cyclosporine a-induced gingival overgrowth in rats.

  Jianbin Guo, Wenyu Wang, Liyan Yao, Fuhua Yan
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  ABSTRACT: Gingival overgrowth (GO) is a common side effect of long-term cyclosporine A (CsA) treatment. The risk factors appraised include drug interactions with calcium channel blockers, age, cyclosporine dose, dental bacterial plaque, duration of treatment, and genetic predisposition. The relationship and mechanism between GO and local inflammation caused by dental bacterial plaque have not been clearly defined. This research was carried out to investigate the histomorphometrical alterations and serum levels of transforming growth factor beta1 (TGF-beta1) in CsA-induced GO with or without local inflammation. Thirty-four male Sprague-Dawley rats were divided into 4 groups: Group I (control); Group II (ligation); Group III (CsA); Group IV (ligation and CsA). After 9 weeks the rats were sacrificed. The morphological examination was made and the histological changes with hematoxylin and eosin (HE) staining were observed. TGF-beta1 levels in serum were detected by enzyme-linked immunosorbent assay (ELISA). We report here that obvious GO are found in Group III and Group IV after CsA treatment, especially those rats with existed gingivitis presented an aggravation of GO. TGF-beta1 levels in CsA-exposed groups were significantly higher than untreated groups, but ligation did not affect TGF-beta1 level. These findings suggest that CsA-induced GO can be exacerbated by local inflammation. TGF-beta1 may be a key factor for the development of GO.
  Inflammation 01/2009; 31(6):399-407.
• Article: Ceftiofur regulates LPS-induced production of cytokines and improves LPS-induced survival rate in mice.

  Xinxin Ci, Hongyu Li, Yu Song, Na An, Qinlei Yu, Fanqin Zeng, Xuming Deng
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  ABSTRACT: The influence of ceftiofur on immune responses has been suggested by results of in vitro studies. This effect was studied using a murine model that measured mortality and early cytokine responses after challenge with endotoxin. To investigate the treatment of endotoxic mice with ceftiofur, mice were pretreated with ceftiofur at different times before and after challenge with a lethal dose of 30 mg/kg lipopolysaccharide (LPS). We found that 20 mg/kg ceftiofur had a significant protective effect and reduced the mortality of mice at early stages. To further understand the mechanism of action of ceftiofur, we examined plasma cytokine levels. Mice treated with LPS alone showed markedly increased plasma levels of TNF-alpha, IL-1beta, IL-6 and IL-10, whereas mice pretreated with 20 mg/kg ceftiofur showed significantly decreased plasma levels of TNF-alpha, IL-1beta and IL-6, but increased plasma levels of IL-10. These results support the idea that ceftiofur has a beneficial effect on LPS-induced endotoxemia caused by LPS through its modulation of cytokine levels. This confirms the effect of ceftiofur for the treatment of endotoxemia, which is caused by a Gram-negative bacterial infection.
  Inflammation 01/2009; 31(6):422-7.
• Article: Effects of all-trans retinoic acid on Th1- and Th2-related chemokines production in monocytes.

  Yu-Chien Tsai, Hui-Wen Chang, Tai-Tsung Chang, Min-Sheng Lee, Yu-Te Chu, Chih-Hsing Hung
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  ABSTRACT: Low vitamin C and reduced alpha-carotene intake are associated with increased asthma risk in children. In addition, mean serum vitamin A concentrations are significantly lower in asthmatic children than in controls. All-trans retinoic acid (ATRA) is a derivative of vitamin A. Macrophage-derived chemokine (MDC) is a T helper cell-type 2 (Th2)-related chemokine involved in the recruitment of Th2 cells toward inflammatory sites. On the other hand, Th1-related chemokine, interferon-inducible protein 10 (IP-10)/CXCL10 is also important in allergic inflammation. Both Th1- and Th2-related chemokines play an important role in allergic asthma. To survey whether ATRA and ascorbic acid effect Th1- and Th2-related chemokine expression in monocytes. To test this, THP-1 cells were pre-treated with ATRA or ascorbic acid and stimulated by lipopolysaccharide (LPS) or poly I:C. Supernatants were measured for Th2-related (MDC) and Th1-related (IP-10) chemokine concentrations by ELISA. The effects of ATRA on mitogen-activated protein kinase (MAPK) and NFkb were evaluated with Western blotting. After stimulation, ATRA significantly down-regulated MDC and IP-10 in a dose-dependent manner. Similarly, ascorbic acid reduced the LPS-induced changes in MDC but only with a high dose. However, asorbic acid had no effect on IP-10 changes either induced by LPS or poly I:C. RT-PCR showed ATRA inhibited IP-10 expression through decreasing the level of transcription. Furthermore, ATRA suppressed the expression of LPS-stimulated c-Raf, MKK1/2 and ERK expression of THP-1 cells. In conclusion, ATRA suppressed Th2- and Th1-related chemokines expression in THP-1 cells, at least in part via the c-Raf-MKK1/2-ERK/MAPK pathway.
  Inflammation 01/2009; 31(6):428-33.