Inhibition of myeloid differentiation 1 specifically in colon with antisense oligonucleotide exacerbates dextran sodium sulfate‐induced colitis

Abstract

Myeloid differentiation 1 (MD‐1), also known as lymphocyte antigen 86 (Ly86), is a soluble protein homologous to MD‐2 and forms a complex with radioprotective 105 (RP105). RP105/MD‐1 complex negatively regulates toll‐like receptor 4 (TLR4) signaling and is involved in several immune disorders. However, the precise role of MD‐1 in inflammatory bowel diseases (IBD) remains poorly understood. To further investigate the involvement of MD‐1 in IBD, we inhibited MD‐1 in colon with antisense oligonucleotide (AS‐ODN) and assessed the effect of MD‐1 inhibition on dextran sodium sulfate (DSS)‐induced colitis. We discovered that MD‐1 protein expression was remarkably decreased in both patients with ulcerative colitis and mice with DSS‐induced colitis. For the first time, we showed that oral administration of MD‐1 AS‐ODN to mice significantly suppressed the MD‐1 protein levels in colon rather than systemic tissues. Subsequently, we found that MD‐1 AS‐ODN treated mice were more susceptible to DSS‐induced colitis based on loss of body weight, colon length, histological scores, and disease activity index. MD‐1 inhibition also significantly enhanced inflammatory cytokines production such as IL‐6 and IL‐1β in colons. Finally, mice treated with MD‐1 AS‐ODN exhibited increased messenger RNA levels of TLR4 and MyD88 after DSS exposure and showed enhanced nuclear factor (NF)‐κB activation compared with the control. Taken together, specifically suppression of MD‐1 in colon tissues with AS‐ODN exacerbates DSS‐induced experimental colitis in mice, which is possibly related to activation of TLR4/NF‐κB signaling.

MD-1 Deficiency Accelerates Myocardial Inflammation and Apoptosis in Doxorubicin-Induced Cardiotoxicity by Activating the TLR4/MAPKs/Nuclear Factor kappa B (NF-κB) Signaling Pathway

“…It is commonly reported that MD-1, also called Ly86, is involved in multiple pathological processes and cellular events, especially the activation of inflammation through the formation of complexes with RP105 [33]. For instance, Chen et al showed that MD-1 loss exacerbates dextran sodium sulfate-elicited colitis [34]. The important roles of RP105/MD-1 in the regulation of HF-caused insulin resistance and inflammation were also demonstrated in a previous study [33].…”

Integrating GWAS with bulk and single-cell RNA-sequencing reveals a role for LY86 in the anti-Candida host response

“…It is known that LY86 forms a complex with Toll-like receptor protein RP105 and is involved in several immune disorders [24][25][26]. Depending on the cell type, this complex has opposite regulatory effects on TLR4 signaling [27,28]; while TLR4 signaling is activated and stimulates proliferation and antibody production in B-cells, it is negatively regulated in myeloid cells.…”

The role of integrins in atherosclerosis complicated with abdominal aortic aneurysm: A bioinformatics study

“…Lymphocyte antigen 86 (LY86), also known as MD-1, can form a complex with radioprotective 105 (PR105) to block the TLR4/MD-2 complex and, thus, attenuate in ammation via the NF-KB signaling pathway [31]. Therefore, an RP105 de ciency can lead to a slower progression of early atherosclerotic plaques [32].…”