title: IL-15 up-regulates the MMP-9 expression levels and induces inflammatory infiltration of macrophages in polymyositis through regulating the NF-kB pathway.
abstract: This study was aimed to research the effects of IL-15 on inducing inflammatory infiltration of macrophages in polymyositis (PM) through the NF-kB pathway, and whether IL-15 was able to further regulate MMP-9 expression levels. Prepared PM cells, collected from the patients suffering from PM, were administered to SD rats. Also, a group of healthy SD rats was undergoing the same treatment as the control group. The test animals were treated with either anti-IL-15, IL-15, MMP-9 siRNA or ERK1/2 inhibitor. The blood toxicological parameters creatine kinase (CK) and CD163 were tested by using ELISA and immunohistochemistry assay. In addition, NF-kB expression in macrophages was measured by immunocytochemical assay. To measure the degree of cell infiltration the Transwell assay was performed. Lastly, western blot and zymography were carried out to compare MMP-9 and ERK expression levels between the two groups, both in vivo and in vitro. The results showed that S-CK, IL-15 and IL-15Rα levels increased rapidly after the conventional treatment was introduced to the PM infected SD rats. The PM model establishment and IL-15 treatment significantly increased the expressions of IL-15Rα, MMP-9, p-ERK and p-IKBα. However, the same effect can be suppressed by using anti-IL-15, MMP-9 siRNA or ERK1/2 inhibitor (P < 0.05). In addition, IL-15 is proved to increase cell migration and nucleus expression of NF-kB in the macrophages. IL-15 is able to significantly regulate the inflammatory infiltration of macrophages in PM patients through affecting the NF-kB pathway and MMP-9 expression levels.
authors.affiliation: Department of Neurological Internal Medicine, Ningbo No.2 Hospital, Ningbo, Zhejiang, 315000, China.
authors.forename: Wang
authors.initials: W
authors.lastname: Yan
authors.affiliation: Department of Neurological Internal Medicine, Ningbo No.2 Hospital, Ningbo, Zhejiang, 315000, China.
authors.forename: Weinv
authors.initials: W
authors.lastname: Fan
authors.affiliation: Department of Neurological Internal Medicine, Ningbo No.2 Hospital, Ningbo, Zhejiang, 315000, China.
authors.forename: Caijing
authors.initials: C
authors.lastname: Chen
authors.affiliation: Department of Neurological Internal Medicine, Ningbo No.2 Hospital, Ningbo, Zhejiang, 315000, China.
authors.forename: Yunqin
authors.initials: Y
authors.lastname: Wu
authors.affiliation: Department of Neurological Internal Medicine, Ningbo No.2 Hospital, Ningbo, Zhejiang, 315000, China.
authors.forename: Zhenyi
authors.initials: Z
authors.lastname: Fan
authors.affiliation: Department of Neurological Internal Medicine, Ningbo No.2 Hospital, Ningbo, Zhejiang, 315000, China.
authors.forename: Jiaqi
authors.initials: J
authors.lastname: Chen
authors.affiliation: Department of Neurological Internal Medicine, Ningbo No.2 Hospital, Ningbo, Zhejiang, 315000, China.
authors.forename: Zhaoying
authors.initials: Z
authors.lastname: Chen
authors.affiliation: Department of Neurological Internal Medicine, Ningbo No.2 Hospital, Ningbo, Zhejiang, 315000, China. Electronic address: chm6420@yeah.net.
authors.forename: Huimin
authors.initials: H
authors.lastname: Chen
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000818:Animals; D002465:Cell Movement / Q000187:drug effects; D004195:Disease Models, Animal; D048049:Extracellular Signal-Regulated MAP Kinases / Q000378:metabolism; D005260:Female; D006728:Hormones / Q000494:pharmacology; D006801:Humans; D007150:Immunohistochemistry; D007249:Inflammation / Q000473:pathology*; D019409:Interleukin-15 / Q000378:metabolism*; D008264:Macrophages / Q000473:pathology*; D008297:Male; D020780:Matrix Metalloproteinase 9 / Q000235:genetics* / Q000378:metabolism; D008875:Middle Aged; D009132:Muscles / Q000201:enzymology / Q000473:pathology; D000072000:NF-KappaB Inhibitor alpha / Q000378:metabolism; D016328:NF-kappa B / Q000378:metabolism*; D010766:Phosphorylation / Q000187:drug effects; D017285:Polymyositis / Q000473:pathology*; D017207:Rats, Sprague-Dawley; D053647:Receptors, Interleukin-15 / Q000378:metabolism; D015398:Signal Transduction / Q000187:drug effects; D015854:Up-Regulation / Q000187:drug effects / Q000235:genetics*
chemical_list: D006728:Hormones; D019409:Interleukin-15; D016328:NF-kappa B; D053647:Receptors, Interleukin-15; D000072000:NF-KappaB Inhibitor alpha; D048049:Extracellular Signal-Regulated MAP Kinases; D020780:Matrix Metalloproteinase 9
keywords: ERK; IKB; IL-15; Inflammatory infiltration; MMP-9; Macrophage; NF-kB; Polymyositis