Article

The IL-17F signaling pathway is involved in the induction of IFN-gamma-inducible protein 10 in bronchial epithelial cells.

First Department of Internal Medicine, Showa University School of Medicine, Tokyo.
Journal of Allergy and Clinical Immunology (impact factor: 11). 07/2007; 119(6):1408-14. DOI:10.1016/j.jaci.2007.02.036
Source: PubMed

ABSTRACT IL-17F is involved in airway inflammation, but its biologic activity and signaling pathway remain incompletely defined. Interferon-gamma-inducible protein 10 (IP-10) is widely expressed and plays a role in airway inflammatory diseases.
We sought to investigate the functional linkage between IL-17F and IP-10 expression in bronchial epithelial cells.
Bronchial epithelial cells were cultured in the presence or absence of IL-17F, and/or a T(H)1 cytokine, T(H)2 cytokines, proinflammatory cytokines, various kinase inhibitors, or a Raf1 dominant-negative mutant to analyze the expression of IP-10. Moreover, the involvement of p90 ribosomal S6 kinase (p90RSK) and cyclic AMP response element-binding protein (CREB) in IL-17F-induced IP-10 expression were investigated.
IL-17F induces the gene and protein expression of IP-10. The addition of IFN-gamma, IL-1beta, and TNF-alpha augmented IL-17F-induced IP-10 expression. The mitogen-activated protein kinase kinase (MEK) inhibitors PD98059, U0126, and Raf1 kinase inhibitor I significantly inhibited its production. In contrast, a p38 inhibitor, a JNK inhibitor, protein kinase C inhibitors, and a phosphatidylinositol 3-kinase inhibitor, showed no inhibitory effect. Furthermore, overexpression of a Raf1 dominant-negative mutant inhibited its expression. Of interest, IL-17F phosphorylated p90RSK and CREB, and transfection of the cells with a short interfering RNA for p90RSK or CREB inhibited its expression, suggesting p90RSK and CREB as novel signaling molecules of IL-17F.
IL-17F is a potent inducer of IP-10 in bronchial epithelial cells through the activation of the Raf1-MEK1/2-extracellular signal-regulated kinase 1/2-p90RSK-CREB pathway, supporting its regulatory role in airway inflammation.
The IL-17F-IP-10 axis might be a novel and critical therapeutic target for airway inflammatory diseases.

0 0
 · 
0 Bookmarks
 · 
23 Views
  • Source
    Article: Increased Serum Circulatory Levels of Interleukin 17F in Type 1 Reactions of Leprosy.
    Sundeep Chaitanya, Mallika Lavania, Ravindra P Turankar, Samuel Raj Karri, U Sengupta
    [show abstract] [hide abstract]
    ABSTRACT: PURPOSE: Leprosy is a chronic infectious disease caused by Mycobacterium leprae affecting mainly skin and peripheral nerves. Acute inflammatory episodes in the borderline immunological spectrum of the disease cause severe nerve and tissue damage leading to deformities. Finding of any serological marker for leprosy reactions will help in prediction of reactions and in early treatment intervention. The objective of this study was to measure the serum circulatory levels of Interleukin 17F (IL 17F) and to correlate the levels with type 1 and type 2 reactional states and with clinico-histopathological spectrum of leprosy. We studied IL 17F to delineate its role and its clinical implications in leprosy reactions. METHODS: Patients were classified based on the Ridley DS and Jopling WH Classification and blood samples (5 ml each) were collected from 80 active untreated leprosy cases in Type 1 reaction (T1R), 21 cases in Type 2 (Erythema Nodosum Leprosum ENL) reaction (T2R), 80 cases without reaction (NR), and 94 non-leprosy cases (NL). Serum was separated and measured for IL 17F levels using ELISA (Commercial Kits, R&D Systems Inc., USA). RESULTS: IL 17F levels were significantly higher in the T1R group when compared to the NR group (pā€‰<ā€‰0.001). The borderline lepromatous group showed the highest levels of IL 17F among the other groups in the disease spectrum. Bacteriological index (BI) showed negative correlation with the IL 17F levels. CONCLUSION: The results specify that serum circulatory levels of IL 17F are elevated during T1Rs in the borderline spectrum of the disease and thus may play a role in the regulation of inflammatory responses associated with reactions in leprosy.
    Journal of Clinical Immunology 07/2012; · 3.08 Impact Factor
  • Source
    Article: Role of interleukin-17F in asthma.
    Mio Kawaguchi, Fumio Kokubu, Junichi Fujita, Shau-Ku Huang, Nobuyuki Hizawa
    [show abstract] [hide abstract]
    ABSTRACT: A new family of cytokines, the interleukin (IL)-17 family, has recently been defined, which reveals unique functions and distinct ligand-receptor signaling systems. This family contains six members, IL-17 (also called IL-17A), IL17B, IL-17C, IL-17D, IL-17E (IL-25) and IL-17F. The IL-17F gene was discovered in 2001, and is located on chromosome 6p12. Notably, among this family, IL-17F has been well characterized both in vitro and in vivo, and has been shown to have a pro-inflammatory role in asthma. IL-17F is clearly expressed in the airway of asthmatics and its expression level is correlated with disease severity. Moreover, a coding region variant (H161R) of the IL-17F gene is inversely associated with asthma and encodes an antagonist for the wild-type IL-17F. IL-17F is able to induce several cytokines, chemokines and adhesion molecules in bronchial epithelial cells, vein endothelial cells, fibroblasts and eosinophils. IL-17F utilizes IL-17RA and IL-17RC as its receptors, and activates the MAP kinase related pathway. IL-17F is derived from several cell types such as Th17 cells, mast cells and basophils, and shows a wide tissue expression pattern including lung. Overexpression of IL-17F gene in the airway of mice is associated with airway neutrophilia, the induction of many cytokines, an increase in airway hyperreactivity, and mucus hypersecretion. Hence, IL-17F may have a crucial role in allergic airway inflammation, and have important therapeutic implications in asthma.
    Inflammation & allergy drug targets. 12/2009; 8(5):383-9.
  • Article: Immunomodulatory effect of NSAID in geriatric patients with acute infection: effects of piroxicam on chemokine/cytokine secretion patterns and levels of heat shock proteins. A double-blind randomized controlled trial. (ISRCTN58517443).
    Ingo Beyer, Rose Njemini, Ivan Bautmans, Christian Demanet, Tony Mets
    [show abstract] [hide abstract]
    ABSTRACT: Inflammation in older persons is associated with frailty, cachexia, and disability. We hypothesized that NSAID treatment in addition to antibiotics in older patients with acute infection might rapidly reduce inflammatory cytokines and might be of therapeutic potential to improve outcomes. A double-blind controlled trial was conducted in geriatric patients admitted for acute infection. Patients were randomized to receive either 10 mg piroxicam or placebo. Patients ā‰„70 years with CRP levels >10 mg/L of acute infectious origin were eligible. Twenty-five cyto-/chemokines as well as heat shock proteins Hsp27 (HSPB1) and Hsp70 (HSPA1A) were measured the first 4 days and then weekly until discharge, with a maximum of 3 weeks. Thirty Caucasian patients were included (median age 84.5 years, 67% female, median CRP 87.5 mg/L). In the piroxicam group, IL-6 and IP-10/CXCL10 decreased significantly during the study period. Relationships between cytokines were disrupted in the piroxicam group: for 12 out of 20 cytokines the number of correlations between changes in serum levels was significantly lower compared to placebo. Serum Hsp70 levels decreased significantly in the piroxicam group, but not in the placebo group. Without heat challenge, intracellular levels of Hsp70 in monocytes decreased in both groups, whereas HsP27 in monocytes increased with piroxicam with a significant difference compared to placebo at 3 weeks. Piroxicam in this setting cannot be considered merely as an anti-inflammatory drug, but rather as an immunomodulator. Further studies are needed to establish whether these effects can change functional outcomes in geriatric patients.
    Cell Stress and Chaperones 11/2011; 17(2):255-65. · 3.01 Impact Factor

Show more

Data provided are for informational purposes only. Although carefully collected, accuracy cannot be guaranteed. The impact factor represents a rough estimation of the journal's impact factor and does not reflect the actual current impact factor. Publisher conditions are provided by RoMEO. Differing provisions from the publisher's actual policy or licence agreement may be applicable.

Keywords

airway inflammation
 
airway inflammatory diseases
 
biologic activity
 
bronchial epithelial cells
 
critical therapeutic target
 
cyclic AMP response element-binding protein
 
IL-17F-induced IP-10 expression
 
Interferon-gamma-inducible protein 10
 
IP-10 expression
 
mitogen-activated protein kinase kinase
 
novel signaling molecules
 
p90 ribosomal S6 kinase
 
phosphatidylinositol 3-kinase inhibitor
 
proinflammatory cytokines
 
protein expression
 
protein kinase C inhibitors
 
Raf1 kinase inhibitor
 
T(H)1 cytokine
 
TNF-alpha augmented IL-17F-induced IP-10 expression
 
various kinase inhibitors