PURPOSE: Myeloid differentiation-2 (MD-2) has been associated with endotoxin and inflammatory disorders because it can recognize lipopolysaccharide (LPS) binding and attenuate Toll-like receptor 4 (TLR4)-mediated signaling. However, its role in allergic inflammation has yet to be clarified. We examined whether single nucleotide polymorphisms (SNPs) in MD-2 promoter can affect MD-2 expression and aimed to clarify the relationship between Der p 2 allergy and SNPs of MD-2 promoter. METHODS: The function of SNPs of MD-2 promoter and the effects of cytokines and immunoglobulin on the secretion and mRNA expression were investigated in 73 allergic subjects with different MD-2 gene promoter variants. Peripheral blood mononuclear cells were cultured with or without LPS in the presence of Dermatophagoides pteronyssinus group 2 allergen (Der p 2), followed by mRNA extraction and cytokine expression analysis. The culture supernatants were collected for cytokine measurement. RESULTS: Patients with the MD-2 promoter SNPs (rs1809441/rs1809442) had increased mRNA expressions of MD-2, epsilon heavy chain of IgE (Cepsilon), and interleukin (IL)-8; however, only MD-2 and IL-8 were further up-regulated after Der p 2 stimulation. Patients with SNPs of MD-2 promoter tended to have high levels of IL-1beta, IL-6, IL-8, IL-10, and tumor necrosis factor (TNF)-alpha after Der p 2 and LPS stimulation. Increased secretions of IL-6, IL-8, and IL-10 were found to be up-regulated by Der p 2 stimulation, and an increased secretion of IFN-gamma and decreased secretion of IL-4 were noted after LPS stimulation. CONCLUSIONS: The high levels of proinflammatory cytokines secreted by Der p 2 were predetermined by MD-2 promoter SNPs (rs1809441/rs1809442). Through cytokine secretion by Der p 2 and LPS, these SNPs may serve as an indicator of the pathological phenotype of Der p 2-induced allergic inflammation.
Cytokines ; Dermatophagoides pteronyssinus ; Humans ; Hypersensitivity ; Immunoglobulin E ; Immunoglobulins ; Inflammation* ; Interleukin-10 ; Interleukin-4 ; Interleukin-6 ; Interleukin-8 ; Interleukins ; Phenotype ; Polymorphism, Single Nucleotide ; RNA, Messenger ; Toll-Like Receptor 4 ; Tumor Necrosis Factor-alpha

Background: Liver regeneration is dependent on the proliferation of hepatocytes. Hepatic progenitorcells are intra-hepatic precursor cells capable of differentiating into hepatocytes or biliary cells.Although liver progenitor cell proliferation during the regenerative process has been observed in animalmodels of severe liver injury, it has never been observed in vivo in humans because it is unethicalto take multiple biopsy specimens for the purpose of studying the proliferation of liver progenitorcells and the roles they play in liver regeneration. Associating liver partition and portal vein ligationfor staged hepatectomy (ALPPS) is a staged procedure for inducing remnant liver hypertrophy sothat major hepatectomy can be performed safely. This staged procedure allows for liver biopsyspecimens to be taken before and after the liver begins to regenerate. Case presentation: The liverprogenitor cell proliferation is observed in a patient undergoing ALPPS for a metastatic hepatictumour. Liver biopsy is acquired before and after ALPPS for the calculation of average number ofliver progenitor cell under high magnification examination by stain of immunomarkers. This is thefirst in vivo evidence of growing liver progenitor cells demonstrated in a regenerating human liver.