title: Substance-P alleviates dextran sulfate sodium-induced intestinal damage by suppressing inflammation through enrichment of M2 macrophages and regulatory T cells.
abstract: Intestinal inflammation alters immune responses in the mucosa and destroys colon architecture, leading to serious diseases such as inflammatory bowel disease (IBD). Thus, regulation of inflammation is regarded as the ultimate therapy for intestinal disease. Substance-P (SP) is known to mediate proliferation, migration, and cellular senescence in a variety of cells. SP was found to mobilize stem cells from bone marrow to the site of injury and to suppress inflammatory responses by inducing regulatory T cells (Tregs) and M2 macrophages. In this study, we explored the effects of SP in a dextran sodium sulfate (DSS)-induced intestine damage model. The effects of SP were evaluated by analyzing crypt structures, proliferating cells within the colon, cytokine secretion profiles, and immune cells population in the spleen/mesenteric lymph nodes in vivo. DSS treatment provoked an inflammatory response with loss of crypts in the intestines of experimental mice. This response was associated with high levels of inflammatory cytokines such as TNF-α and IL-17, and low levels of Tregs and M2 macrophages, leading to severely damaged tissue structure. However, SP treatment inhibited inflammatory responses by modulating cytokine production as well as the balance of Tregs/Th 17 cells and the M1/M2 transition in lymphoid organs, leading to accelerated tissue repair. Collectively, our data indicate that SP can promote the regeneration of tissue following damage by DSS treatment, possibly by modulating immune response. Our results propose SP as a candidate therapeutic for intestine-related inflammatory diseases.
authors.affiliation: College of Medicine/East-West Medical Research Institute, Kyung Hee University, Kyungheedae-ro, Dongdaemun-gu, Seoul 02447, Republic of Korea. Electronic address: hshong@khu.ac.kr.
authors.forename: Hyun Sook
authors.initials: HS
authors.lastname: Hong
authors.affiliation: Department of Medicine, Graduate School, Kyung Hee University, Kyungheedae-ro, Dongdaemun-gu, Seoul 02447, Republic of Korea.
authors.forename: Dae Yeon
authors.initials: DY
authors.lastname: Hwang
authors.affiliation: Graduate School of Biotechnology & Department of Genetic Engineering, College of Life Science, Kyung Hee University, Seochun-dong, Kiheung-ku, Yong In 441-706, Republic of Korea.
authors.forename: Ju Hyeong
authors.initials: JH
authors.lastname: Park
authors.affiliation: Graduate School of Biotechnology & Department of Genetic Engineering, College of Life Science, Kyung Hee University, Seochun-dong, Kiheung-ku, Yong In 441-706, Republic of Korea.
authors.forename: Suna
authors.initials: S
authors.lastname: Kim
authors.affiliation: Department of Medicine, Graduate School, Kyung Hee University, Kyungheedae-ro, Dongdaemun-gu, Seoul 02447, Republic of Korea.
authors.forename: Eun Jung
authors.initials: EJ
authors.lastname: Seo
authors.affiliation: Graduate School of Biotechnology & Department of Genetic Engineering, College of Life Science, Kyung Hee University, 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; D016264:Dextran Sulfate / Q000633:toxicity*; D007249:Inflammation / Q000139:chemically induced / Q000188:drug therapy / Q000378:metabolism / Q000473:pathology; D015212:Inflammatory Bowel Diseases / Q000139:chemically induced / Q000188:drug therapy* / Q000378:metabolism* / Q000473:pathology; D020381:Interleukin-17 / Q000378:metabolism; D007413:Intestinal Mucosa / Q000378:metabolism*; D007422:Intestines / Q000473:pathology; D008264:Macrophages / Q000378:metabolism* / Q000473:pathology; D008297:Male; D051379:Mice; D013373:Substance P / Q000494:pharmacology*; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism
chemical_list: D020381:Interleukin-17; D014409:Tumor Necrosis Factor-alpha; D013373:Substance P; D016264:Dextran Sulfate
keywords: Intestinal damages; M2 macrophages; Regulatory T cell; Substance-P