title: Clearance of Propionibacterium acnes by kupffer cells is regulated by osteopontin through modulating the expression of p47phox.
abstract: Osteopontin (OPN) is a cytokine with multiple functions, including the regulation of innate immune response. However, the detailed function and mechanism of OPN in host defense against invaded microorganisms remain unclear. In this report, we revealed that OPN could affect the clearance of Propionibacterium acnes in kupffer cells. In a murine model of P. acnes induced hepatic granuloma, OPN-deficient mice or wild-type (WT) mice treated with anti-OPN mAb exhibited more hepatic granuloma formation than WT mice. Increased infiltration of intrahepatic leukocytes, higher expression of TLRs, and significantly upregulated level of proinflammatory cytokines of liver tissue were observed in OPN-deficient mice after P. acnes challenge. Moreover, in vitro assay showed that kupffer cells isolated from OPN(-/-) mice exhibited impairment in clearance of P. acnes. Kupffer cells isolated from OPN(-/-) mice showed reduced level of NADPH oxidase-mediated reactive oxygen species (ROS) in response to P. acnes, which was regulated by NADPH oxidase subunit p47phox. Further investigation revealed that OPN interaction with αvβ3 integrin activated PI3K and ERK signal pathways, leading to the expression of p47phox. Taken together, these data demonstrated an important role of OPN in enhancing the antimicrobial innate immune response by modulation of bacterium clearance activity in kupffer cells.
authors: School of Medicine, Shanghai Jiao Tong University, 227 South Chongqing Road, Shanghai 200025, People's Republic of China.
authors: Haiou
authors: H
authors: Yang
authors: Huaizu
authors: H
authors: Guo
authors: Kexing
authors: K
authors: Fan
authors: Bo
authors: B
authors: Zhang
authors: Lei
authors: L
authors: Zhao
authors: Sheng
authors: S
authors: Hou
authors: Weizhu
authors: W
authors: Qian
authors: Dapeng
authors: D
authors: Zhang
authors: Hao
authors: H
authors: Wang
authors: Jianxing
authors: J
authors: Dai
authors: Yajun
authors: Y
authors: Guo
mesh_terms: D000818:Animals; D015153:Blotting, Western; D002469:Cell Separation; D005434:Flow Cytometry; D015870:Gene Expression; D005786:Gene Expression Regulation / Q000276:immunology*; D016908:Gram-Positive Bacterial Infections / Q000276:immunology* / Q000378:metabolism / Q000473:pathology; D006099:Granuloma / Q000276:immunology / Q000382:microbiology / Q000473:pathology; D007728:Kupffer Cells / Q000276:immunology* / Q000378:metabolism; D008099:Liver / Q000276:immunology / Q000382:microbiology / Q000473:pathology; D051379:Mice; D018345:Mice, Knockout; D019255:NADPH Oxidases / Q000096:biosynthesis* / Q000276:immunology; D053495:Osteopontin / Q000276:immunology* / Q000378:metabolism; D011425:Propionibacterium acnes / Q000276:immunology; D017382:Reactive Oxygen Species / Q000276:immunology / Q000378:metabolism; D020133:Reverse Transcriptase Polymerase Chain Reaction; D015398:Signal Transduction / Q000276:immunology
chemical_list: D017382:Reactive Oxygen Species; D053495:Osteopontin; D019255:NADPH Oxidases; C060505:neutrophil cytosolic factor 1