IL-4 Downregulates IL-1β and IL-6 and Induces GATA3 in Psoriatic Epidermal Cells: Route of Action of a Th2 Cytokine.
نویسندگان
چکیده
Clinical improvement of psoriasis induced by IL-4 treatment has been ascribed to changes in dermal inflammatory cells, such as activation of Th2 cells and tolerization of dendritic cells by suppressing IL-23 production. The pathologic epidermal alterations in psoriatic lesional skin include increased epidermal expression of IL-1β, IL-6, S100A7, and human β-defensin 2 (hBD2) and a downregulated expression of the epidermal transcription factor GATA3. Effects of IL-4 on the epidermal compartment of psoriasis lesions were not previously investigated. Therefore, we investigated whether IL-4 directly affects abovementioned psoriatic markers in the epidermal compartment. We cultured freshly isolated psoriatic epidermal cells, whole psoriatic and healthy skin biopsies, human keratinocytes and Langerhans cells with IL-4. The secretion of IL-1β and IL-6 by psoriatic epidermal cells was inhibited by IL-4 via transcriptional and posttranscriptional mechanisms, respectively. In normal skin, IL-4 inhibited IL-1β- and IL-17A-induced hBD2 expression in vitro. In addition, IL-4 reduced the protein expression of hBD2 in psoriatic skin biopsies and induced phospho-STAT6 protein. Epidermal GATA3 mRNA and protein were significantly upregulated by IL-4 in epidermal cells and keratinocytes. Our data argue that IL-4 improves psoriasis not only via modification/induction of Th2 cells and type II dendritic cells, but also via direct inhibition of inflammatory cytokines in resident IL-4R-expressing epidermal cells and thereby alters the psoriatic skin phenotype toward a healthy skin phenotype.
منابع مشابه
IL-4 Downregulates IL-1b and IL-6 and Induces GATA3 in Psoriatic Epidermal Cells: Route of Action of a Th2 Cytokine
متن کامل
IL-4 Can Inhibit IL-17 Production in Collagen Induced Arthritis
Background: IL-4 is a cytokine that induces differentiation of naive helper T cells into Th2 cells. Once activated by IL-4, Th2 cells subsequently produce additional IL-4. Objective: To examine the effect of IL-4 on IL-17 production and its effect in Collagen- Induced Arthritis (CIA) mice. Method: In this study, a chicken collagen-II-induced experimental arthritis (CIA) model was used in DBA/1 ...
متن کاملEffect of Shiga Toxin And Its Subunits On Cytokine Induction in Different Cell Lines
Shiga toxins (Stxs) are bacterial virulence factors produced by Shigella dysenteriae serotype 1 and Escherichia coli strains. Stxs are critical factors for the development of diseases such as severe bloody diarrhea and hemolytic uremic syndrome. Additionally, Stxs trigger the secretion of pro- inflammatory cytokines and chemokines, particularly in monocytes or macrophages. The inflammatory cyto...
متن کاملPiper nigrum Fruit Extract Prevents TMA-Induced Allergic Contact Dermatitis by Regulating Th2 Cytokine Production
Allergic contact dermatitis (ACD) remains a leading skin disease in many countries. In this study, we investigated the preventive effect of Piper nigrum fruit extract (PFE) on trimellitic anhydride (TMA)-induced dermatitis and its potential mechanism of action. Oral administration of PFE and prednisolone (PS) significantly suppressed TMA-induced increases in ear, epidermal thickness, and infilt...
متن کاملبررسی سیتوکینهایTh1-Th2 در سطح سلولی در بیماران مبتلا به سپسیس و سپسیس شدید
Background: Sepsis is the leading cause of death in critically ill patients throughout the world. The incidence is increasing despite the major advances in the development of antimicrobial agents and other supportive treatments. Based on multiple studies, it has been shown that patient outcome depends on Th1 and Th2 cytokine response. Moreover, whenever the Th2 response is predominant, the seps...
متن کاملذخیره در منابع من
با ذخیره ی این منبع در منابع من، دسترسی به آن را برای استفاده های بعدی آسان تر کنید
عنوان ژورنال:
- Journal of immunology
دوره 195 4 شماره
صفحات -
تاریخ انتشار 2015