Objective To explore the mechanism by which the triggering receptor expressed on Myeloid cells-like 4(TREML4)regulates nuclear factor-kappaB(NF-κB)pathway mediates neutrophil extracellular traps(NETs)aggravating rheumatoid arthritis(RA).Methods RA model was induced by subcutaneous injection of Freund adjuvant and bovine collagen type Ⅱ in DBA/1J mice.We used phorbol 12-myristate 13-acetate(PMA)to induce neutrophils to form NETs.We observed the degree of joint swelling and other morphological indicators,used hematoxylin-eosin staining(HE)staining to observe the pathology of the ankle joint,used enzyme-linked immunosorbent assay(ELISA)to measure the levels of inflammatory factors interleukin-1β(IL-1β),interleukin-6(IL-6)and tumor necrosis factor-α(TNF-α)in serum,used western blot to detect the expression of myeloperoxidase(MPO)and citrullinated histone H3(CitH3)for assess the release of NETs in the ankle joint of mice,used western blot to detect the expression of TREML4 and NF-κB pathway-associated proteins nuclear factor kappa B inhibitor α(IκBα)and NF-κB p65,used immunofluorescence to detect the distribution of MPO and CitH3 in neutrophils to assess the formation of NETs.Results Compared with the control group,the RA group exhibited joint swelling,bone erosion,excessive infiltration of immune cells and cartilage damage,and the serum inflammatory fac-tors IL-6,TNF-α and IL-1β were significantly increased(P＜0.01),the expression of IκBα was significantly decreased(P＜0.01),and the expression of NF-κB p65 was significantly increased(P＜0.01).Compared with control group,the number of NETs formed by neutrophils in PMA group was significantly increased,the expression of TREML4 and NF-κB p65 was significantly increased(P＜0.01),and the expression of IκBα was significantly decreased(P＜0.01).Compared with the PMA+si-NC group,the number of NETs formed by neutrophils in the PMA+si-TREML4group was significantly reduced(P＜0.01),the expression of TREML4 and NF-κB p65 was significantly decreased(P＜0.01),and the expression of IκBα was significantly increased(P＜0.01).Conclusion TREML4 can regulate the formation of NETs mediated by NF-κB pathway to aggravate RA.

Objective To explore the mechanism by which the triggering receptor expressed on Myeloid cells-like 4(TREML4)regulates nuclear factor-kappaB(NF-κB)pathway mediates neutrophil extracellular traps(NETs)aggravating rheumatoid arthritis(RA).Methods RA model was induced by subcutaneous injection of Freund adjuvant and bovine collagen type Ⅱ in DBA/1J mice.We used phorbol 12-myristate 13-acetate(PMA)to induce neutrophils to form NETs.We observed the degree of joint swelling and other morphological indicators,used hematoxylin-eosin staining(HE)staining to observe the pathology of the ankle joint,used enzyme-linked immunosorbent assay(ELISA)to measure the levels of inflammatory factors interleukin-1β(IL-1β),interleukin-6(IL-6)and tumor necrosis factor-α(TNF-α)in serum,used western blot to detect the expression of myeloperoxidase(MPO)and citrullinated histone H3(CitH3)for assess the release of NETs in the ankle joint of mice,used western blot to detect the expression of TREML4 and NF-κB pathway-associated proteins nuclear factor kappa B inhibitor α(IκBα)and NF-κB p65,used immunofluorescence to detect the distribution of MPO and CitH3 in neutrophils to assess the formation of NETs.Results Compared with the control group,the RA group exhibited joint swelling,bone erosion,excessive infiltration of immune cells and cartilage damage,and the serum inflammatory fac-tors IL-6,TNF-α and IL-1β were significantly increased(P＜0.01),the expression of IκBα was significantly decreased(P＜0.01),and the expression of NF-κB p65 was significantly increased(P＜0.01).Compared with control group,the number of NETs formed by neutrophils in PMA group was significantly increased,the expression of TREML4 and NF-κB p65 was significantly increased(P＜0.01),and the expression of IκBα was significantly decreased(P＜0.01).Compared with the PMA+si-NC group,the number of NETs formed by neutrophils in the PMA+si-TREML4group was significantly reduced(P＜0.01),the expression of TREML4 and NF-κB p65 was significantly decreased(P＜0.01),and the expression of IκBα was significantly increased(P＜0.01).Conclusion TREML4 can regulate the formation of NETs mediated by NF-κB pathway to aggravate RA.