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Inactivation of TMEM106A promotes lipopolysaccharide-induced inflammation via the MAPK and NF-κB signaling pathways in macrophages.
Zhang, X; Feng, T; Zhou, X; Sullivan, P M; Hu, F; Lou, Y; Yu, J; Feng, J; Liu, H; Chen, Y.
Afiliación
  • Zhang X; Department of Immunology, Peking University School of Basic Medical Sciences, Beijing, China.
  • Feng T; NHC Key Laboratory of Medical Immunology, Peking University, Beijing, China.
  • Zhou X; Beijing Key Laboratory for Pediatric Diseases of Otolaryngology, Head and Neck Surgery, MOE Key Laboratory of Major Diseases in Children, Beijing Pediatric Research Institute, Beijing Children's Hospital, Capital Medical University, National Center for Children's Health (NCCH), Beijing, China.
  • Sullivan PM; Weill Institute for Cell and Molecular Biology, Department of Molecular Biology and Genetics, Cornell University, Ithaca, NY, USA.
  • Hu F; Weill Institute for Cell and Molecular Biology, Department of Molecular Biology and Genetics, Cornell University, Ithaca, NY, USA.
  • Lou Y; Weill Institute for Cell and Molecular Biology, Department of Molecular Biology and Genetics, Cornell University, Ithaca, NY, USA.
  • Yu J; Weill Institute for Cell and Molecular Biology, Department of Molecular Biology and Genetics, Cornell University, Ithaca, NY, USA.
  • Feng J; Medical and Healthy Analytical Center, Peking University, Beijing, China.
  • Liu H; Department of Immunology, Peking University School of Basic Medical Sciences, Beijing, China.
  • Chen Y; NHC Key Laboratory of Medical Immunology, Peking University, Beijing, China.
Clin Exp Immunol ; 203(1): 125-136, 2021 01.
Article en En | MEDLINE | ID: mdl-33006758
Pattern recognition receptors, such as Toll-like receptors (TLRs), play an important role in the host defense against invading microbial pathogens. Their activation must be precisely regulated, as inappropriate activation or overactivation of TLR signaling pathways may result in inflammatory disorders, such as septic shock or autoimmune diseases. TMEM106A is a type II transmembrane protein constitutively expressed in macrophages. Our current study demonstrated that TMEM106A levels were increased in macrophages upon lipopolysaccharide (LPS) stimulation, as well as in the peripheral monocytes of patients with sepsis. Tmem106a knockout mice were more sensitive to lipopolysaccharide (LPS)-induced septic shock than wild-type mice. Further experiments indicated that Tmem106a ablation enhanced the expression of CD80, CD86 and major histocompatibility complex (MHC)-II in mouse macrophages upon LPS stimulation, accompanied with up-regulation of tumor necrosis factor (TNF)-α, interleukin (IL)-6, interferon (IFN)-ß and inducible nitric oxide synthase (iNOS), indicating the activation of macrophages and polarization towards the M1 inflammatory phenotype. Moreover, elevated mitogen-activated protein kinase (MAPK) and nuclear factor kappa B (NF-κB) signaling were found to be involved in the LPS-induced inflammatory response in Tmem106a-/- macrophages. However, this effect was largely abrogated by macrophage deletion in Tmem106a-/- mice. Therefore, deficiency of Tmem106a in macrophages may enhance the M1 polarization in mice, resulting in inflammation. This suggests that TMEM106A plays an important regulatory role in maintaining macrophage homeostasis.
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Lipopolisacáridos / FN-kappa B / Macrófagos Peritoneales / Sistema de Señalización de MAP Quinasas / Proteínas Supresoras de Tumor / Quinasas MAP Reguladas por Señal Extracelular Límite: Animals Idioma: En Revista: Clin Exp Immunol Año: 2021 Tipo del documento: Article País de afiliación: China Pais de publicación: Reino Unido
Texto completo
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Lipopolisacáridos / FN-kappa B / Macrófagos Peritoneales / Sistema de Señalización de MAP Quinasas / Proteínas Supresoras de Tumor / Quinasas MAP Reguladas por Señal Extracelular Límite: Animals Idioma: En Revista: Clin Exp Immunol Año: 2021 Tipo del documento: Article País de afiliación: China Pais de publicación: Reino Unido