title: Phospholipase A2 inhibits cisplatin-induced acute kidney injury by modulating regulatory T cells by the CD206 mannose receptor.
abstract: Previously, we found that Foxp3-expressing CD4(+) regulatory T (Treg) cells attenuate cisplatin-induced acute kidney injury in mice and that bee venom and its constituent phospholipase A2 (PLA2) are capable of modulating Treg cells. Here we tested whether PLA2 could inhibit cisplatin-induced acute kidney injury. As a result of treatment with PLA2, the population of Treg cells was significantly increased, both in vivo and in vitro. PLA2-injected mice showed reduced levels of serum creatinine, blood urea nitrogen, renal tissue damage, and pro-inflammatory cytokine production upon cisplatin administration. These renoprotective effects were abolished by depletion of Treg cells. Furthermore, PLA2 bound to CD206 mannose receptors on dendritic cells, essential for the PLA2-mediated protective effects on renal dysfunction. Interestingly, PLA2 treatment increased the secretion of IL-10 in the kidney from normal mice. Foxp3(+)IL-10(+) cells and CD11c(+)IL-10(+) cells were increased by PLA2 treatment. The anticancer effects of repeated administrations of a low dose of cisplatin were not affected by PLA2 treatment in a tumor-bearing model. Thus, PLA2 may prevent inflammatory responses in cisplatin-induced acute kidney injury by modulating Treg cells and IL-10 through the CD206 mannose receptor.
authors.affiliation: Department of Physiology, College of Korean Medicine, Kyung Hee University, Dongdaemoon-gu, Seoul, Republic of Korea.
authors.forename: Hyunseong
authors.initials: H
authors.lastname: Kim
authors.affiliation: Department of Physiology, College of Korean Medicine, Kyung Hee University, Dongdaemoon-gu, Seoul, Republic of Korea.
authors.forename: Hyojung
authors.initials: H
authors.lastname: Lee
authors.affiliation: Department of Physiology, College of Korean Medicine, Kyung Hee University, Dongdaemoon-gu, Seoul, Republic of Korea.
authors.forename: Gihyun
authors.initials: G
authors.lastname: Lee
authors.affiliation: Department of Physiology, College of Korean Medicine, Kyung Hee University, Dongdaemoon-gu, Seoul, Republic of Korea.
authors.forename: Hyunil
authors.initials: H
authors.lastname: Jang
authors.affiliation: Soram Korean Medicine Hospital, Gangnam-gu, Seoul, Republic of Korea.
authors.forename: Sung-Su
authors.initials: SS
authors.lastname: Kim
authors.affiliation: Department of Physiology, College of Korean Medicine, Kyung Hee University, Dongdaemoon-gu, Seoul, Republic of Korea.
authors.forename: Heera
authors.initials: H
authors.lastname: Yoon
authors.affiliation: Department of Physiology, College of Korean Medicine, Kyung Hee University, Dongdaemoon-gu, Seoul, Republic of Korea.
authors.forename: Geun-Hyung
authors.initials: GH
authors.lastname: Kang
authors.affiliation: Department of Obstetrics and Gynecology, College of Korean Medicine, Kyung Hee University, Dongdaemoon-gu, Seoul, Republic of Korea.
authors.forename: Deok-Sang
authors.initials: DS
authors.lastname: Hwang
authors.affiliation: Department of Physiology, College of Korean Medicine, Kyung Hee University, Dongdaemoon-gu, Seoul, Republic of Korea.
authors.forename: Sun Kwang
authors.initials: SK
authors.lastname: Kim
authors.affiliation: Cancer Preventive Material Development Research Center, Kyung Hee University, Dongdaemoon-gu, Seoul, Republic of Korea.
authors.forename: Hwan-Suck
authors.initials: HS
authors.lastname: Chung
authors.affiliation: Department of Physiology, College of Korean Medicine, Kyung Hee University, Dongdaemoon-gu, Seoul, Republic of Korea.
authors.forename: Hyunsu
authors.initials: H
authors.lastname: Bae
mesh_terms: D058186:Acute Kidney Injury / Q000139:chemically induced / Q000201:enzymology / Q000235:genetics / Q000276:immunology / Q000473:pathology / Q000517:prevention & control*; D000818:Animals; D000893:Anti-Inflammatory Agents / Q000494:pharmacology*; D000970:Antineoplastic Agents; D002478:Cells, Cultured; D002945:Cisplatin; D019610:Cytoprotection; D004195:Disease Models, Animal; D004305:Dose-Response Relationship, Drug; D018836:Inflammation Mediators / Q000378:metabolism; D016753:Interleukin-10 / Q000172:deficiency / Q000235:genetics; D007668:Kidney / Q000187:drug effects* / Q000201:enzymology / Q000276:immunology / Q000473:pathology; D037181:Lectins, C-Type / Q000172:deficiency / Q000235:genetics / Q000378:metabolism*; D008213:Lymphocyte Activation / Q000187:drug effects*; D008223:Lymphoma / Q000188:drug therapy / Q000473:pathology; D008297:Male; D000090323:Mannose Receptor; D037241:Mannose-Binding Lectins / Q000172:deficiency / Q000235:genetics / Q000378:metabolism*; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D054467:Phospholipases A2 / Q000494:pharmacology*; D011485:Protein Binding; D011956:Receptors, Cell Surface / Q000172:deficiency / Q000235:genetics / Q000378:metabolism*; D015398:Signal Transduction / Q000187:drug effects; D050378:T-Lymphocytes, Regulatory / Q000187:drug effects* / Q000201:enzymology / Q000276:immunology; D013997:Time Factors
chemical_list: D000893:Anti-Inflammatory Agents; D000970:Antineoplastic Agents; C556062:IL10 protein, mouse; D018836:Inflammation Mediators; D037181:Lectins, C-Type; D000090323:Mannose Receptor; D037241:Mannose-Binding Lectins; D011956:Receptors, Cell Surface; D016753:Interleukin-10; D054467:Phospholipases A2; D002945:Cisplatin