Induction of thymic stromal lymphopoietin production by nonanoic acid and exacerbation of allergic inflammation in mice.
BACKGROUND
Thymic stromal lymphopoietin (TSLP) plays critical roles in the induction and exacerbation of allergic diseases. We tested various chemicals in the environment and found that xylene and 1,2,4-trimethylbenzene induced the production of TSLP in vivo. These findings prompted us to search for additional chemicals that induce TSLP production. In this study, we examined whether fatty acids could induce the production of TSLP in vivo and exacerbate allergic inflammation.


METHODS
Various fatty acids and related compounds were painted on the ear lobes of mice and the amount of TSLP in the homogenate of ear lobe tissue was determined. The effects of nonanoic acid on allergic inflammation were also examined.


RESULTS
Octanoic acid, nonanoic acid, and decanoic acid markedly induced TSLP production, while a medium-chain aldehyde and alcohol showed only weak activity. Nonanoic acid induced the production of TSLP with a maximum at 24 h. TSLP production was even observed in nonanoic acid-treated C3H/HeJ mice that lacked functional toll-like receptor 4. The aryl hydrocarbon receptor agonist β-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.


CONCLUSIONS
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.
Graduate School of Pharmaceutical Sciences, Tohoku University, Miyagi, Japan.
Saori
S
Yamashita
Ryosuke
R
Segawa
Nozomi
N
Satou
Masahiro
M
Hiratsuka
Warren J
WJ
Leonard
Noriyasu
N
Hirasawa
D000438:Alcohols / Q000008:administration & dosage; D000447:Aldehydes / Q000008:administration & dosage; D000818:Animals; D016207:Cytokines / Q000235:genetics / Q000378:metabolism*; D018450:Disease Progression; D005227:Fatty Acids / Q000009:adverse effects*; D005786:Gene Expression Regulation / Q000187:drug effects / Q000235:genetics; D006967:Hypersensitivity / Q000276:immunology*; D007136:Immunoglobulins / Q000378:metabolism; D007249:Inflammation / Q000139:chemically induced / Q000276:immunology*; D051379:Mice; D008809:Mice, Inbred C3H; D018345:Mice, Knockout; D010853:Picryl Chloride / Q000008:administration & dosage; D018336:Receptors, Aryl Hydrocarbon / Q000819:agonists; D018121:Receptors, Cytokine / Q000235:genetics / Q000378:metabolism; D012867:Skin / Q000187:drug effects / Q000473:pathology*; D051197:Toll-Like Receptor 4 / Q000235:genetics; D019324:beta-Naphthoflavone / Q000008:administration & dosage; D000094632:Thymic Stromal Lymphopoietin
D000438:Alcohols; D000447:Aldehydes; D016207:Cytokines; D005227:Fatty Acids; D007136:Immunoglobulins; D018336:Receptors, Aryl Hydrocarbon; D018121:Receptors, Cytokine; D051197:Toll-Like Receptor 4; C410591:Tslpr protein, mouse; D019324:beta-Naphthoflavone; C008776:pelargonic acid; D010853:Picryl Chloride; D000094632:Thymic Stromal Lymphopoietin; C000721967:TSLP protein, mouse