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- Title
iRhom2 deficiency reduces sepsis-induced mortality associated with the attenuation of lung macrophages in mice.
- Authors
Kim, Jihye; Kim, Jee Hyun; Kim, Younghoon; Lee, Jooyoung; Lee, Hyun Jung; Koh, Seong-Joon; Im, Jong Pil; Kim, Joo Sung
- Abstract
Sepsis has a high mortality rate and leads to multi-organ failure, including lung injury. Inactive rhomboid protease family protein (iRhom2) has been identified as accountable for the release of TNF-α, a crucial mediator in the development of sepsis. This study aimed to evaluate the role of iRhom2 in sepsis and sepsis-induced acute lung injury (ALI). TNF-α and IL-6 secretion in vitro by peritoneal macrophages from wild-type (WT) and iRhom2 knoukout (KO) mice was assessed by enzyme-linked immunosorbent assay. Cecal ligation and puncture (CLP)-induced murine sepsis model was used for in vivo experiments. To evaluate the role of iRhom2 deficiency on survival during sepsis, both WT and iRhom2 KO mice were monitored for 8 consecutive days following the CLP. For histologic and biochemical examination, the mice were killed 18 h after CLP. iRhom2 deficiency improved the survival of mice after CLP. iRhom2 deficiency decreased CD68 macrophage infiltration in lung tissues. Multiplex immunohistochemistry revealed that the proportion of Ki-67 CD68 macrophages was significantly lower in iRhom2 KO mice than that in WT mice after CLP. Moreover, CLP-induced release of TNF-α and IL-6 in the serum were significantly inhibited by iRhom2 deficiency. iRhom2 deficiency reduced NF-kB p65 and IκBα phosphorylation after CLP. iRhom2 deficiency reduces sepsis-related mortality associated with attenuated macrophage infiltration and proliferation in early lung injury. iRhom2 may play a pivotal role in the pathogenesis of sepsis and early stage of sepsis-induced ALI. Thus, iRhom2 may be a potential therapeutic target for the management of sepsis and sepsis-induced ALI.
- Subjects
SEPSIS; PERITONEAL macrophages; ENZYME-linked immunosorbent assay; MACROPHAGES; LUNGS; MICE
- Publication
Histochemistry & Cell Biology, 2024, Vol 162, Issue 5, p415
- ISSN
0948-6143
- Publication type
Academic Journal
- DOI
10.1007/s00418-024-02318-5