untreated, nonanoic acid alone, and ovalbumin alone groups

untreated, nonanoic acid alone, and ovalbumin alone groups. == EXACERBATION OF PICL-INDUCED ALLERGIC AMD 3465 Hexahydrobromide INFLAMMATION BY NONANOIC ACID AND THE INVOLVEMENT OF TSLP == We investigated the possibility that nonanoic acid exacerbated PiCl-induced allergic dermatitis via TSLP production. toll-like receptor 4. The aryl hydrocarbon receptor agonist -naphthoflavone did not induce TSLP production. Nonanoic acid promoted sensitization to ovalbumin, resulting in an enhancement in the cutaneous anaphylactic response. In addition, painting of nonanoic acid after the sensitization augmented picryl chloride-induced thickening of the ear, which was reversed in TSLP receptor-deficient mice. == Conclusion == Nonanoic acid and certain fatty acids induced TSLP production, resulting in the exacerbation of allergic inflammation. We propose that TSLP-inducing chemical compounds such as nonanoic acid be recognized as chemical allergo-accelerators. Keywords:Thymic stromal lymphopoietin, nonanoic acid, fatty acid, ovalbumin, picryl chloride == INTRODUCTION == Thymic stromal lymphopoietin (TSLP) was recently identified as a master cytokine regulating the induction of allergies1,2. TSLP is an IL-7-like cytokine3that is produced mainly by AMD 3465 Hexahydrobromide epithelial cells, and plays important roles in the regulation of immune responses by inducing the maturation and activation of dendritic cells4,5,6, lymphocytes, basophil precursors, and fibrocytes7. The production of TSLP is increased at AMD 3465 Hexahydrobromide inflamed sites in patients with severe asthma5, atopic dermatitis8, and allergic rhinitis9. The crucial roles of TSLP in allergic inflammation were demonstrated using transgenic mice. Allergic inflammation in an animal model of asthma and the exacerbation of allergic dermatitis were significantly suppressed in TSLP receptor-deficient mice10,11. Various environmental factors trigger the production of TSLP12. For example, stimulants of toll-like receptor 2 or 4 in the presence of tumor necrosis factor (TNF)- and Th2 cytokines such as interleukin (IL)-4 induced the production of TSLP in synovial fibroblasts13and skin keratinocytesin vitro14. In addition, several chemical compounds induced TSLP production. Phthalate ester was shown to induce TSLP productionin vivo15,16. Having examined the activity of various chemical compounds in the environment, we found that xylene and 1,2,4-trimethylbenzene strongly induced TSLP productionin vivo11. These compounds were not allergens, but exacerbated the effects of contact sensitizers, picryl chloride (PiCl)11, and fluoresceinisothiocyanate (FITC)15,16. Thus, the Mouse monoclonal to GATA4 AMD 3465 Hexahydrobromide production of TSLP caused by chemical compounds may be important in promoting sensitization to antigens. These findings prompted us to search for additional chemical compounds that induce TSLP production. Various fatty acids are contained in soaps and plants, and sometimes cause contact dermatitis. Therefore, in this study, we investigated whether fatty acids could induce the production of TSLPin vivoand exacerbate allergic inflammation. == METHODS == == ANIMALS == Male BALB/c, C57BL/6, C3H/HeN, and C3H/HeJ mice (5 weeks old) were purchased from SLC (Shizuoka, Japan). The generation of TSLP receptor-knockout mice (C57BL/6 background) was described previously17. Mice were treated in accordance with procedures approved by the Animal Ethics Committee of Tohoku University, Sendai, Japan. == ASSAY OF TSLP, IL-4, AND TNF- AMD 3465 Hexahydrobromide PRODUCTION BY CHEMICALS == -naphthoflavone was purchased from Sigma-Aldrich (St. Louis, MO, U.S.A.). Pentanoic acid, hexanoic acid, heptanoic acid, octanoic acid, nonanoic acid, decanoic acid, dodecanoic acid, tetradecanoic acid, n-nonane, 1-nonanol, 1-nonanal, 1-decanal, 1-octanal, 2-nonanone, and picryl chloride were purchased from Wako Pure Chemical Ind. (Osaka, Japan). Decanoic acid, dodecanoic acid, tetradecanoic acid, and -naphthoflavone were dissolved in acetone. Acetone was used to dilute nonanoic acid. Twenty microliters of each solution or liquid chemical was painted on the ear lobes of mice. Ear lobe tissue was then punched out (diameter 5 mm) at a specified time and weighed. Tissue samples were homogenized at 4C in a 10 vol of phosphate-buffered saline by a Beads Cell Disrupter (Precellys 24, Bertin Technology, France). The concentrations of TSLP, IL-4, and TNF- in the supernatant of the homogenate were determined by ELISA (TSLP; R & D Systems,.