title: Mitogen-activated protein kinase phosphatase-1 expression in macrophages             is controlled by lymphocytes during macrophage activation.
abstract: The viewpoints on the control of innate immune cells by the adaptive immune             system during sepsis remain controversial. Mitogen-activated protein kinase phosphatase-1             (MKP-1) is essential to the negative control of innate immunity and suppresses             the activation of macrophages by inhibiting activated mitogen-activated protein             kinase (MAPK). The purpose of the current study was to observe inflammatory response             and macrophage activation in mice with severe combined immunodeficiency (SCID)             with endotoxemia and to determine the role of MKP-1 in the control of macrophage             activation by the adaptive immune system. Endotoxemia was induced in wild-type             and SCID mice by an intraperitoneal injection of lipopolysaccharide (LPS), and             all of the SCID mice died. SCID mice produced more inflammatory cytokines than             BALB/c mice systemically and locally. TNF-α mRNA expression was higher and MKP-1             mRNA expression was lower in peritoneal macrophages (PMa) from SCID mice compared             to PMa from wild-type mice after and even before LPS injection. Thioglycollate-stimulated             PMa from wild-type mice were stimulated with LPS in vitro in the presence or absence             of pan-T cells. The levels of TNF-α and IL-6 were higher in the supernatants from             PMa cultured alone compared to PMa co-cultured with pan-T cells, and PMa MKP-1             mRNA and protein expression were higher when PMa were co-cultured with pan-T cells.             Therefore, pan-T cells can up-regulate MKP-1 expression in macrophages and inhibit             the secretion of inflammatory cytokines secretion by macrophages. In SCID mice,             lymphocyte deficiency, especially T cell deficiency, causes insufficient MKP-1             expression in macrophages, which can be responsible for the severe inflammation             and bad prognosis of septic SCID mice. MKP-1 plays an important role in the control             of macrophage activation by the adaptive immune system.
authors.affiliation: Ministry of Education Key Laboratory of Child Development and Disorders, Children's Hospital of Chongqing Medical University, Chongqing, PR China.
authors.forename: Chong
authors.initials: C
authors.lastname: Luo
authors.forename: Xiqiang
authors.initials: X
authors.lastname: Yang
authors.forename: Lan
authors.initials: L
authors.lastname: Yao
authors.forename: Liping
authors.initials: L
authors.lastname: Jiang
authors.forename: Wei
authors.initials: W
authors.lastname: Liu
authors.forename: Xin
authors.initials: X
authors.lastname: Li
authors.forename: Lijia
authors.initials: L
authors.lastname: Wang
mesh_terms: D000704:Analysis of Variance; D000818:Animals; D001202:Ascitic Fluid / Q000737:chemistry / Q000378:metabolism; D054638:Dual Specificity Phosphatase 1 / Q000096:biosynthesis* / Q000235:genetics / Q000378:metabolism; D019446:Endotoxemia; D005260:Female; D007249:Inflammation; D016753:Interleukin-10 / Q000097:blood / Q000235:genetics / Q000378:metabolism; D053208:Kaplan-Meier Estimate; D008070:Lipopolysaccharides / Q000276:immunology; D008214:Lymphocytes / Q000187:drug effects / Q000201:enzymology* / Q000378:metabolism; D008262:Macrophage Activation / Q000276:immunology / Q000502:physiology*; D008264:Macrophages / Q000187:drug effects / Q000201:enzymology* / Q000378:metabolism; D051379:Mice; D008807:Mice, Inbred BALB C; D016513:Mice, SCID; D008856:Microscopy, Fluorescence; D016133:Polymerase Chain Reaction; D014409:Tumor Necrosis Factor-alpha / Q000097:blood / Q000235:genetics / Q000378:metabolism
chemical_list: D008070:Lipopolysaccharides; D014409:Tumor Necrosis Factor-alpha; D016753:Interleukin-10; D054638:Dual Specificity Phosphatase 1