NMI and IFP35 are key DAMP molecules in inflammatory bowel diseases

Abstract

Background & AimN‐myc and STAT interactor (NMI) and interferon‐induced protein 35 (IFP35) are damage‐associated molecular patterns (DAMPs), that mediate pro‐inflammatory reactions upon cell or tissue damage. Excessive signaling mediated by DAMP molecules can lead to several chronic inflammatory diseases. Here we investigated potential roles for NMI and IFP35 in the pathogenesis of inflammatory bowel diseases (IBD) including Crohn’s disease and ulcerative colitis.MethodDifferentially expressed genes (DEG) were identified in the colonic mucosa of CD and UC in comparison with controls by the gene expression microarray dataset that was validated by quantitative real‐time polymerase chain reaction and immunohistochemistry.ResultNMI and IFP35 were highly elevated in the colonic mucosa of both CD and UC patients, compared to healthy controls. The fold changes of NMI in the colonic epithelium of CD and UC were 1.78 (P < 0.05) and 1.79 (P <0.05), respectively; while the fold changes of IFP35 were 1.73(P<0.05 ) and 1.74 (P<0.05), respectively in CD and UC. More importantly, the expression of NMI and IFP35 decreased to normal levels in the responders after infliximab treatment, but remained elevated in the non‐responders of the infliximab treatment. Compared to the controls, the fold changes of NMI in CD and UC non‐responder was 1.92 (P<0.05) and 1.65(P<0.05), respectively; the fold changes of IFP35 in CD and UC non‐responders were 1.64(P<0.05) and 1.4(P<0.05), respectively. Consistently, the expression levels of the downstream molecules including TLR4, TNF and IL‐6 paralleled and positively associated with those of the NMI/IFP35 (P < 0.05).ConclusionsOur observations suggest that DAMP molecules NMI/IFP35 may mediate the early events of the IBD pathogenesis. We are confirming these observations at RNA and protein levels. Future plans include intervention studies using therapeutic antibodies to block NMI/IFP35 activities in IBD animal models. Considering that many DAMP molecules are effective targets in the treatment of chronic inflammatory diseases, we are optimistic about the future clinical application of NMI/IFP35 for the treatment of IBD.Support or Funding Information1.National Natural Science Foundation of China 81774152, 31200986, 41530105, 81770571,81970452. 2.Guangzhou laboratory clinical innovation project 2018GZR0201005. 3.National Postdoctoral Program for Innovative Talents of China BX20190393. 4.Natural Science Foundation of Shanghai 16ZR1449800. 5.the University at Buffalo Community of Excellence in Genome, Environment and Microbiome (GEM).