title: Osteopontin depletion decreases inflammation and gastric epithelial proliferation during Helicobacter pylori infection in mice.
abstract: Osteopontin (OPN) is a multifunctional protein that plays a role in many physiological and pathological processes, including inflammation and tumorigenesis. Here, we investigated the involvement of OPN in Helicobacter pylori (HP)-induced gastritis using OPN knockout (KO) mice and OPN knockdown (KD) cell lines. HP-infected OPN KO mice showed significantly reduced gastritis compared with wild-type (WT) mice with decreased infiltration of macrophages and a reduction in HP-induced upregulation of IL-1β, TNF-α, and IFN-γ. HP-exposed OPN KD gastric cancer cells and macrophage-like cells showed an attenuated induction of these cytokines. We also demonstrated a reduction in the migration of monocytic and macrophage-like cells toward conditioned media harvested from HP-exposed OPN KD gastric cancer cells as well as reduced migration ability of OPN KD cells itself. In addition, HP-infected OPN KO mice showed decreased epithelial cell proliferation compared with HP-infected WT mice, in association with a reduction in MAPK pathway activation. OPN KD gastric cancer cell lines also showed lower proliferative activity and reduced MAPK activation than shRNA control cells after HP co-culture or after IL-1β and TNF-α treatment. Taken together, these results indicate that OPN exerts a considerable influence on HP-induced gastritis by modulating the production of cytokines and contributing to macrophage infiltration. Moreover, OPN-mediated activation of the MAPK pathway in gastric epithelial cells might contribute to epithelial changes following HP infection.
authors: 1] Department of Veterinary Pathology, College of Veterinary Medicine, Seoul National University, Seoul, Korea [2] National Cancer Center, Goyang, Gyeonggi, Korea.
authors: Jun Won
authors: JW
authors: Park
authors: Department of Veterinary Pathology, College of Veterinary Medicine, Seoul National University, Seoul, Korea.
authors: Su Hyung
authors: SH
authors: Lee
authors: Department of Veterinary Pathology, College of Veterinary Medicine, Seoul National University, Seoul, Korea.
authors: Du Min
authors: du M
authors: Go
authors: National Cancer Center, Goyang, Gyeonggi, Korea.
authors: Hark Kyun
authors: HK
authors: Kim
authors: College of Veterinary Medicine, Chungnam National University, Daejeon, Korea.
authors: Hyo-Jung
authors: HJ
authors: Kwon
authors: Department of Veterinary Pathology, College of Veterinary Medicine, Seoul National University, Seoul, Korea.
authors: Dae-Yong
authors: DY
authors: Kim
mesh_terms: D000818:Animals; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000502:physiology*; D016207:Cytokines; D005260:Female; D005753:Gastric Mucosa / Q000378:metabolism*; D055786:Gene Knockout Techniques; D016481:Helicobacter Infections / Q000378:metabolism*; D016480:Helicobacter pylori; D006801:Humans; D007249:Inflammation / Q000378:metabolism*; D008264:Macrophages; D051379:Mice; D008810:Mice, Inbred C57BL; D053495:Osteopontin / Q000235:genetics / Q000378:metabolism*; D015854:Up-Regulation
chemical_list: D016207:Cytokines; C506896:Spp1 protein, mouse; D053495:Osteopontin