title: 5-Aminosalicylic acid inhibits inflammatory responses by suppressing JNK and p38 activity in murine macrophages.
abstract: BACKGROUND
  5-Aminosalicylic acid (5-ASA), as an anti-inflammatory drug, has been extensively used for the treatment of mild to moderate active ulcerative colitis (UC), but the possible mechanisms of action remain unclear.
  
  
  OBJECTIVE
  To investigate the effects of 5-ASA on the production of inflammatory mediators by murine macrophages stimulated with lipopolysaccharide (LPS), and determine the underlying pharmacological mechanism of action.
  
  
  METHODS
  The levels of nitric oxide (NO) and interleukin-6 (IL-6) were measured by Varioskan Flash and IL-6 Enzyme-Linked Immunosorbent Assay sets. Real time quantitative polymerase chain reaction was used to determine the level of induced nitric oxide synthase (iNOS). The effects of 5-ASA on iNOS, the c-Jun N-terminal kinases (JNKs), p38 and nuclear factor (NF)-κB signaling pathways were examined using western blotting.
  
  
  RESULTS
  5-ASA suppressed the production of NO and IL-6, and also decreased the expression of iNOS in LPS-induced RAW264.7 cells. 5-ASA inhibited the phosphorylation of JNKs and p38, but did not block NF-κB activation at all doses tested.
  
  
  CONCLUSIONS
  The results indicated that the anti-inflammatory effect of 5-ASA was mainly regulated by the inhibition of the JNKs, p38 pathways rather than NF-κB pathway. Further research is required to clarify the detailed mechanism of the action.
authors.affiliation: a School of Pharmaceutical Science of Shanxi Medical University , Taiyuan , Shanxi , People's Republic of China.
authors.forename: Tingli
authors.initials: T
authors.lastname: Qu
authors.affiliation: b Chemical and Biological Engineering College of Taiyuan University of Science and Technology , Taiyuan , Shanxi , People's Republic of China.
authors.forename: Erbing
authors.initials: E
authors.lastname: Wang
authors.affiliation: a School of Pharmaceutical Science of Shanxi Medical University , Taiyuan , Shanxi , People's Republic of China.|c Fuyong People's Hospital , Shenzhen , Guangdong , People's Republic of China.
authors.forename: Baofen
authors.initials: B
authors.lastname: Jin
authors.affiliation: d Department of Pharmacology , Fenyang College Shanxi Medical University , Fenyang , Shanxi , People's Republic of China.
authors.forename: Weiping
authors.initials: W
authors.lastname: Li
authors.affiliation: a School of Pharmaceutical Science of Shanxi Medical University , Taiyuan , Shanxi , People's Republic of China.
authors.forename: Ruiling
authors.initials: R
authors.lastname: Liu
authors.affiliation: a School of Pharmaceutical Science of Shanxi Medical University , Taiyuan , Shanxi , People's Republic of China.
authors.forename: Zheng-Bao
authors.initials: ZB
authors.lastname: Zhao
mesh_terms: D000818:Animals; D004305:Dose-Response Relationship, Drug; D007249:Inflammation / Q000188:drug therapy / Q000276:immunology / Q000473:pathology; D015850:Interleukin-6 / Q000276:immunology; D048670:MAP Kinase Kinase 4; D020935:MAP Kinase Signaling System / Q000187:drug effects* / Q000276:immunology; D008264:Macrophages / Q000276:immunology* / Q000473:pathology; D019804:Mesalamine / Q000494:pharmacology*; D051379:Mice; D009569:Nitric Oxide / Q000276:immunology; D052247:Nitric Oxide Synthase Type II / Q000276:immunology; D000067996:RAW 264.7 Cells; D048051:p38 Mitogen-Activated Protein Kinases / Q000276:immunology*
chemical_list: D015850:Interleukin-6; C577686:interleukin-6, mouse; D009569:Nitric Oxide; D019804:Mesalamine; D052247:Nitric Oxide Synthase Type II; C496317:Nos2 protein, mouse; D048051:p38 Mitogen-Activated Protein Kinases; D048670:MAP Kinase Kinase 4
keywords: 5-Aminosalicylic acid; JNK; NO; lipopolysaccharide; p38