Glowacka E, Lewkowicz P, Rotsztejn H et al.IL-8, IL-12 and IL-10 cytokines generation by neutrophils, fibroblasts and neutrophils- fibroblasts interaction in psoriasis. Adv Med Sci 55:254-60

Department of Clinical Immunology, Polish Mother's Memorial Hospital - Research Institute, Lodz, Poland.
Advances in Medical Sciences (Impact Factor: 1.11). 10/2010; 55(2):254-60. DOI: 10.2478/v10039-010-0037-0
Source: PubMed


Psoriasis is a common skin disease affecting about 1-3% of the world population. Many types of cells, including lymphocytes, dendritics APCs (antigen presenting cells), NKT (natural killer T) cells, neutrophils, keratinocytes and fibroblasts are involved in the pathogenesis of psoriasis.The aim of our study was to assess in psoriatic patients the production of IL-8, IL-10 and IL-12 cytokines by neutrophils, fibroblasts and fibroblasts - neutrophils interaction.
The production of IL-8, IL-10 and IL-12 cytokines was evaluated in supernatants after cells incubation for 21 h in culture medium alone and in medium in the presence of IL-8 or TNF-α. Concentrations of IL-8, IL-10, IL-12 were measured by enzyme-linked immunosorbent assay (ELISA) method using commercially available kits.
Our results demonstrate that fibroblasts are not able to produce IL-10 and IL-12 but they generate IL-8. The amount of IL-8 depends on the site of derivation of fibroblasts and on the stimuli. Neutrophils released IL-8, IL-12 (at a lower level in psoriatic patients) and IL-10 but only in the case of healthy donors and at a very low concentration. Moreover, we observed higher concentrations of IL-12 and IL-8 in supernatants as a result of fibroblasts-neutrophils interaction in psoriatic patients.
Our results suggest that fibroblasts take part in the inflammatory reaction in psoriasis via cytokines or direct interaction with neutrophils. Fibroblasts probably do not exert any anti-inflammatory effect.

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    • "Fibroblast cells have been demonstrated to take part in the inflammatory reaction in psoriasis (Glowacka et al., 2010; Schirmer et al., 2010). Although not typical immune cells, fibroblast cells have been demonstrated to express FOXP3 and immune cytokines/receptors, including CCL3 and CCR5, upon stimulation (Konishi et al., 1996; Maurer and von Stebut, 2004; Zhu Shen et al., submitted). "
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    ABSTRACT: The connection between infections and acute guttate psoriasis (AGP) outbreaks/chronic plaque psoriasis (CPP) exacerbation has been known for years. Impaired function of FOXP3+Tregs in psoriasis has been identified. However, the mechanisms behind these two observations have not been fully interpreted. In the present study, we provide evidence to support chemokine CCL3 as one of the vital links between infections and FOXP3 stability in the psoriatic microenvironment. We found that serum CCL3, strongly induced by microorganism infections including streptococcus, was closely correlated with FOXP3 levels in CD4+CD25+T cells of patients with psoriasis. CCL3 manipulated FOXP3 stability in a concentration-dependent bidirectional manner. High-concentration CCL3 decreased FOXP3 stability by promoting FOXP3's degradation through K48-linkage ubiquitination. This degradation was mainly dependent on upregulation of Serine 473 phosphorylation of the PKBα/Akt1 isoform, and almost independent of mTORC1 (mammalian target of rapamycin complex 1) activity. On the other hand, low-concentration CCL3 could enhance FOXP3 stability by the maintenance of the PKC pathway and the restriction of the PKB/Akt pathway. We further demonstrated that enhancing FOXP3 stability by low-concentration CCL3 attributed, at least partly, to the prevention of cytoplasmic Sin1, a vital component of mTORC2, nuclear translocation. Our results suggest vital roles for CCL3-mTORC2-isoform PKB/Akt1 S473 phosphorylation axis in FOXP3+Tregs and the development of psoriasis.Journal of Investigative Dermatology advance online publication, 6 December 2012; doi:10.1038/jid.2012.333.
    Journal of Investigative Dermatology 12/2012; 133(2). DOI:10.1038/jid.2012.333 · 7.22 Impact Factor
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    • "IL-12 also has been well characterized as a suppressor of Th2 cytokines, such as IL-4 and IL-10 [3]. For its roles in immune responses, IL-12 has been implicated in the pathogenesis of several diseases, including inflammatory diseases such as rheumatoid arthritis [4], psoriasis [5], and Crohn's disease [6] and oral conditions such as periodontitis [7]. The aim of this paper is to discuss the mechanisms associated to the IL-12-related immune response in tooth periapical lesions. "
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    ABSTRACT: Periapical lesions are inflammatory conditions of tooth periapical tissues, triggered by dental pulp infection and characterized by exudation of immune cells to the affected tissues and production of inflammatory mediators such as cytokines. The inflammatory periapical reaction is mainly driven by Th1, Th2, and Th17 responses, and such polarization may modulate progression of the disease and expression of bone proresorptive cytokines. IL-12 is a potent inducer of IFN-γ production, which stimulates Th1 effector cells. Many evidences have shown a positive correlation between the bone resorptive cytokine IL-1β and the production of IL-12 and IFN-γ. Furthermore, IL-12 may have a potential role in the release of bone resorptive mediators and blockade of Th2 cytokines, affecting the progression of periapical bone loss. Nevertheless, IL-12 and IFN-γ have also been described as suppressors of osteoclast differentiation and activation, favoring bone maintenance. This paper focuses on the controversial roles of IL-12 in periapical lesions.
    Clinical and Developmental Immunology 01/2010; 2010(4):327417. DOI:10.1155/2010/327417 · 2.93 Impact Factor
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    ABSTRACT: Sepsis is a deadly immunological disorder and its pathophysiology is still poorly understood. We aimed to determine if specific pro-inflammatory and anti-inflammatory cytokines can be used as diagnostic and therapeutic targets for sepsis. Recent publications in the MEDLINE database were searched for articles regarding the clinical significance of inflammatory cytokines in sepsis. In response to pathogen infection, pro-inflammatory cytokines [interleukin-6 (IL-6), IL-8, IL-18 and tumor necrosis factor-α (TNF-α)] and anti-inflammatory cytokine (IL-10) increased in patients with sepsis. Importantly, a decrease in IL-6 was associated with a better prognosis and overproduction of IL-10 was found to be the main predictor of severity and fatal outcome. Both pro-inflammatory and anti-inflammatory cytokines constitute a double-edged sword in sepsis; on one hand they are critical to eliminate the infection while on the other, excessive production can cause tissue and organ damage. Increase in cytokines such as IL-6, Il-8, IL-10, IL-18 and TNF-α may have implications in diagnosis and treatment of sepsis.
    In vivo (Athens, Greece) 11/2013; 27(6):669-84. · 0.97 Impact Factor
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