title: Substance P ameliorates collagen II-induced arthritis in mice via suppression of the inflammatory response.
abstract: Current rheumatoid arthritis (RA) therapies such as biologics inhibiting pathogenic cytokines substantially delay RA progression. However, patient responses to these agents are not always complete and long lasting. This study explored whether substance P (SP), an 11 amino acids long endogenous neuropeptide with the novel ability to mobilize mesenchymal stem cells (MSC) and modulate injury-mediated inflammation, can inhibit RA progression. SP efficacy was evaluated by paw swelling, clinical arthritis scoring, radiological analysis, histological analysis of cartilage destruction, and blood levels of tumor necrosis factor-alpha (TNF-α) interleukin (IL)-10, and IL-17 in vivo. SP treatment significantly reduced local inflammatory signs, mean arthritis scores, degradation of joint cartilage, and invasion of inflammatory cells into the synovial tissues. Moreover, the SP treatment markedly reduced the size of spleens enlarged by excessive inflammation in CIA, increased IL-10 levels, and decreased TNF-α and IL-17 levels. Mobilization of stem cells and induction of T(reg) and M2 type macrophages in the circulation were also increased by the SP treatment. These effect of SP might be associated with the suppression of inflammatory responses in RA and, furthermore, blockade of RA progression. Our results propose SP as a potential therapeutic for autoimmune-related inflammatory diseases.
authors.affiliation: College of Medicine, East-West Medical Research Institute, Kyung Hee University, 1, Hoegi-dong, Dongdaemun-gu, Seoul 130-702, Republic of Korea.
authors.forename: Hyun Sook
authors.initials: HS
authors.lastname: Hong
authors.affiliation: Graduate School of Biotechnology & Department of Genetic Engineering, College of Life Science, Kyung Hee University Global Campus, Seochun-dong, Kiheung-ku, Yong In 441-706, Republic of Korea. Electronic address: ysson@khu.ac.kr.
authors.forename: Youngsook
authors.initials: Y
authors.lastname: Son
mesh_terms: D000818:Animals; D000893:Anti-Inflammatory Agents / Q000627:therapeutic use; D001169:Arthritis, Experimental / Q000188:drug therapy* / Q000276:immunology / Q000473:pathology; D001172:Arthritis, Rheumatoid / Q000276:immunology / Q000473:pathology / Q000628:therapy; D018450:Disease Progression; D006801:Humans; D007165:Immunosuppression Therapy; D016753:Interleukin-10 / Q000097:blood; D020381:Interleukin-17 / Q000097:blood; D008264:Macrophages / Q000276:immunology; D008297:Male; D059630:Mesenchymal Stem Cells / Q000276:immunology; D051379:Mice; D008811:Mice, Inbred DBA; D013373:Substance P / Q000276:immunology* / Q000627:therapeutic use*; D050378:T-Lymphocytes, Regulatory / Q000276:immunology; D014409:Tumor Necrosis Factor-alpha / Q000097:blood
chemical_list: D000893:Anti-Inflammatory Agents; C556062:IL10 protein, mouse; D020381:Interleukin-17; D014409:Tumor Necrosis Factor-alpha; D016753:Interleukin-10; D013373:Substance P
keywords: Autoimmune disease; Inflammation; Rheumatoid arthritis; Substance P