title: Acetyl salicylic acid inhibits Th17 airway inflammation via blockade of IL-6 and IL-17 positive feedback.
abstract: T-helper (Th)17 cell responses are important for the development of neutrophilic inflammatory disease. Recently, we found that acetyl salicylic acid (ASA) inhibited Th17 airway inflammation in an asthma mouse model induced by sensitization with lipopolysaccharide (LPS)-containing allergens. To investigate the mechanism(s) of the inhibitory effect of ASA on the development of Th17 airway inflammation, a neutrophilic asthma mouse model was generated by intranasal sensitization with LPS plus ovalbumin (OVA) and then challenged with OVA alone. Immunologic parameters and airway inflammation were evaluated 6 and 48 h after the last OVA challenge. ASA inhibited the production of interleukin (IL)-17 from lung T cells as well as in vitro Th17 polarization induced by IL-6. Additionally, ASA, but not salicylic acid, suppressed Th17 airway inflammation, which was associated with decreased expression of acetyl-STAT3 (downstream signaling of IL-6) in the lung. Moreover, the production of IL-6 from inflammatory cells, induced by IL-17, was abolished by treatment with ASA, whereas that induced by LPS was not. Altogether, ASA, likely via its acetyl moiety, inhibits Th17 airway inflammation by blockade of IL-6 and IL-17 positive feedback.
authors.affiliation: Department of Life Science and Division of Molecular and Life Sciences, Pohang University of Science and Technology (POSTECH), Pohang, Republic of Korea.
authors.forename: Hyung-Geun
authors.initials: HG
authors.lastname: Moon
authors.forename: Chil Sung
authors.initials: CS
authors.lastname: Kang
authors.forename: Jun-Pyo
authors.initials: JP
authors.lastname: Choi
authors.forename: Dong Sic
authors.initials: DS
authors.lastname: Choi
authors.forename: Hyun Il
authors.initials: HI
authors.lastname: Choi
authors.forename: Yong Wook
authors.initials: YW
authors.lastname: Choi
authors.forename: Seong Gyu
authors.initials: SG
authors.lastname: Jeon
authors.forename: Joo-Yeon
authors.initials: JY
authors.lastname: Yoo
authors.forename: Myoung Ho
authors.initials: MH
authors.lastname: Jang
authors.forename: Yong Song
authors.initials: YS
authors.lastname: Gho
authors.forename: Yoon-Keun
authors.initials: YK
authors.lastname: Kim
mesh_terms: D000818:Animals; D001241:Aspirin / Q000494:pharmacology / Q000627:therapeutic use*; D016764:Cell Polarity / Q000187:drug effects / Q000276:immunology; D025461:Feedback, Physiological / Q000187:drug effects*; D007371:Interferon-gamma / Q000172:deficiency / Q000378:metabolism; D020381:Interleukin-17 / Q000378:metabolism* / Q000494:pharmacology; D015850:Interleukin-6 / Q000096:biosynthesis / Q000378:metabolism*; D008070:Lipopolysaccharides / Q000494:pharmacology; D008168:Lung / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D051379:Mice; D008810:Mice, Inbred C57BL; D011014:Pneumonia / Q000188:drug therapy* / Q000276:immunology* / Q000473:pathology; D058504:Th17 Cells / Q000187:drug effects / Q000276:immunology* / Q000473:pathology; D053773:Transforming Growth Factor beta1 / Q000494:pharmacology
chemical_list: D020381:Interleukin-17; D015850:Interleukin-6; D008070:Lipopolysaccharides; D053773:Transforming Growth Factor beta1; D007371:Interferon-gamma; D001241:Aspirin