Expression and significance of myeloid differentiation factor 88 in non-small cell lung carcinoma and normal paracancerous tissues.

We studied the expression level of myeloid differentiation factor 88 (MyD88) in non-small cell lung carcinoma (NSCLC) and normal paracancerous tissues, to determine its relationship with clinical pathological characteristics and prognosis. In total, 82 NSCLC patients who had received surgical treatment in our hospital between September 2008 and December 2013 were selected for this study. Another 82 normal paracancerous lung tissue samples were used as controls. All patients had complete clinical records, and they were followed-up for 5 years. The expression level of MyD88 protein was detected by immunohistochemical assay. The positive expression rate of MyD88 in NSCLC tissues (62.2%) was markedly higher than that in normal tissues (10.9%), and was independent of patient characteristics such as age, gender, pathological pattern, history of smoking, and tumor size (P > 0.05). However, MyD88 expression was significantly correlated with degree of differentiation, clinical staging, and lymphatic metastasis (P < 0.05), and was negatively correlated with prognosis. The 5-year survival rate of patients with positive MyD88 expression was significantly lower than that of patients without positive expression (P < 0.05). MyD88 was expressed at a higher level in NSCLC tissues and was closely associated with poor prognosis. MyD88 may be a novel eligible target for treating NSCLC.

Relevance of the myeloid differentiation factor 88 (MyD88) on RANKL, OPG, and nod expressions induced by TLR and IL-1R signaling in bone marrow stromal cells.

The myeloid differentiation factor 88 (MyD88) plays a pivotal role in Toll-like receptor (TLR)- and interleukin-1 receptor (IL-1R)-induced osteoclastogenesis. We examined the role of MyD88 on p38 mitogen-activated protein kinase (MAPK) and nuclear factor kappa-light-chain-enhancer of activated B cell (NF-κB) activation and nucleotide-binding oligomerization domain (Nod) induction by lipopolysaccharide (LPS) and IL-1 beta, and their effect on receptor activator of NF-κB ligand (RANKL) and osteoprotegerin (OPG) production in bone marrow stromal cell (BMSC). RANKL, Nod1, Nod2, NF-κB, and p38 protein levels were determined by Western blot. Nod2 was stimulated with muramyl dipeptide (MDP) prior to TLR4 stimulation with LPS. MyD88 deficiency markedly inhibited RANKL expression after LPS stimulation and increased OPG messenger RNA (mRNA) production. Also, MyD88 was necessary for NF-κB and p38 MAPK activation. MDP alone did not induce RANKL and OPG expressions; however, when combined with LPS, their expressions were significantly increased (p < 0.05). Our results support that MyD88 signaling has a pivotal role in osteoclastogenesis thought NF-κB and p38 activation. Nod2 and especially Nod1 levels were influenced by MyD88.

Increased TLR2 expression in patients with type 1 diabetes: evidenced risk of microalbuminuria.

OBJECTIVE: To study the activation of an inflammatory cascade through leukocyte mRNA expression of TLR2, TLR4, MyD88, and pro-inflammatory cytokines in individuals with childhood onset type 1 diabetes. DESIGN AND METHODS: Seventy-six type 1 diabetic patients and 100 normoglycemic subjects (NG) 6 to 20 years old were recruited. Type 1 diabetic patients (DM1) were considered to have good (DM1G) or poor (DM1P) glycemic control according to the values of glycated hemoglobin. TLR2, TLR4, MyD88, interleukin -1ß (IL-1ß), IL-6, and tumor necrosis factor alpha (TNF-α) mRNA expressions were measured in peripheral blood leukocytes (PBL) by real-time polymerase chain reaction (PCR). Urea, creatinine, albumin, and total protein serum levels were determined. Urinary albumin-to-creatinine ratio (ACR) was calculated. RESULTS: DM1 and DM1P patients showed higher glycated hemoglobin (10 and 11%, respectively) and serum glucose concentrations (208 and 226 mg/dL, respectively) compared to NG (Glycated hemoglobin: 7% and glucose: 76 mg/dL) (p < 0.05). PBL mRNA expressions of TLR2, MyD88, IL-1ß, IL-6, and TNF-α were higher in DM1 and TLR2, IL-1ß, and IL-6 expressions were higher in DMP1 compared to NG (p < 0.05). In DM1, serum albumin and total protein were lower, while serum urea and ACR were higher in comparison to NG (p < 0.05). However, these differences compared to NG were more pronounced in DM1P, which included nine individuals with microalbuminuria. CONCLUSIONS: Increased mRNA expression of TLR2, MyD88, and pro-inflammatory cytokines in leukocytes of patients with childhood onset type 1 diabetes indicates the development of a TLR2-mediated pro-inflammatory process, which may also be associated with an early inflammatory process in the kidney and the occurrence of microalbuminuria.