Cytokines ; physiology ; Humans ; Interferon-gamma ; physiology ; Interleukin-1 ; physiology ; Interleukin-10 ; physiology ; Interleukin-12 ; physiology ; Interleukin-6 ; physiology ; Interleukin-8 ; physiology ; Rotavirus Infections ; immunology ; Tumor Necrosis Factor-alpha ; physiology

Animals ; Humans ; Interleukin-6 ; physiology ; Liver Cirrhosis ; physiopathology ; Mice ; Pulmonary Fibrosis ; physiopathology ; Rats

Hypertrophic scar is a pathological repair result of excessive accumulation of extracellular matrix after skin damage, which affects the appearance and function of patients with varying degrees. The degree of scar formation is directly related to the strength of inflammatory reaction during wound healing, and excessive or prolonged inflammatory response increases the incidence of hypertrophic scars. Interleukin-6 (IL-6) is a pleiotropic cytokine that is involved in regulating the fibrotic network composed of fibroblasts, macrophages, keratinocytes, and vascular endothelial cells, and is closely related to the formation of hypertrophic scars. This article reviews the role of IL-6 and its signaling pathway in hypertrophic scar formation.
Cicatrix, Hypertrophic/pathology* ; Endothelial Cells/metabolism* ; Fibroblasts/metabolism* ; Humans ; Interleukin-6 ; Skin/pathology* ; Wound Healing/physiology*

The shivering and nonshivering thermogenesis in skeletal muscles is important for maintaining body temperature in a cold environment. In addition to nervous-humoral regulation, adipose tissue was demonstrated to directly respond to cold in a cell-autonomous manner to produce heat. However, whether skeletal muscle can directly respond to low temperature in an autoregulatory manner is unknown. Transient receptor potential (TRP) channels TRPM8 and TRPA1 are two important cold sensors. In the current study, we found TRPM8 was expressed in mouse skeletal muscle tissue and C2C12 myotubes by RT-PCR. After exposure to 33 °C for 6 h, the gene expression pattern of C2C12 myotubes was significantly changed which was evidenced by RNA-sequencing. KEGG-Pathway enrichment analysis of these differentially expressed genes showed that low temperature changed several important signaling pathways, such as IL-17, TNFα, MAPK, FoxO, Hedgehog, Hippo, Toll-like receptor, Notch, and Wnt signaling pathways. Protein-protein interaction network analysis revealed that IL-6 gene was a key gene which was directly affected by low temperature in skeletal muscle cells. In addition, both mRNA and protein levels of IL-6 were increased by 33 °C exposure in C2C12 myotubes. In conclusion, our findings demonstrated that skeletal muscle cells could directly respond to low temperature, characterized by upregulated expression of IL-6 in skeletal muscle cells.
Animals ; Cold Temperature ; Interleukin-6/metabolism* ; Mice ; Muscle Fibers, Skeletal/metabolism* ; Muscle, Skeletal/physiology* ; Temperature

T helper (Th) 17 cells are a kind of Th cell subset, and are distinct from the Th1 and Th2 cells and produce interleukin-17A (IL-17A, IL-17). Th17 cells have a mechanism of independent differentiation and developmental regulation. The differentiation and cytokine secretion of Th17 cells are regulated by TGF-β, IL-6, IL-23 and orphan nuclear receptor (RORγt). IL-17A induces pro-inflammatory cytokines and chemokines, mediating neutrophil recruitment. Increasing evidence implicated involvement of Th17 cells in anti-glomerular basement membrane disease, lupus nephritis and pauciimmune glomerulonephritis. In this review, we discussed the discovery of Th17 subset, its properties, its relationship with other Th subsets and involvement of Th17 cells in glomerulonephritis.
Animals ; Glomerulonephritis ; immunology ; Humans ; Interleukin-17 ; metabolism ; physiology ; Interleukin-23 Subunit p19 ; physiology ; Interleukin-6 ; physiology ; Nuclear Receptor Subfamily 1, Group F, Member 3 ; physiology ; Th17 Cells ; immunology ; metabolism ; Transforming Growth Factor beta ; physiology

Accumulating evidence has revealed that brain iron concentrations increase with aging, and the choroid plexus (CP) may be at the basis of iron-mediated toxicity and the increase in inflammation and oxidative stress that occurs with aging. The mechanism involves not only hepcidin, the key hormone in iron metabolism, but also iron-related proteins and signaling-transduction molecules, such as IL-6 and signal transducer and activator of transcription 3 (Stat3). The aim of the present study was to investigate the correlation between the IL-6/Stat3 signaling pathway and hepcidin at the CP in normal aging. Quantitative real time PCR and Western blot were used to determine the alterations in specific mRNA and corresponding protein changes at the CP at ages of 3, 6, 9, 12, 15, 18, 21, 24, 27, 30, 33 and 36 months in Brown-Norway/Fischer (B-N/F) rats. The results demonstrated that hepcidin mRNA level at the CP kept stable in young rats (from 3 to 18 months), and increased with aging (from 21 to 36 months). The alterations of IL-6/p-Stat3 mRNA and protein expressions in normal aging were in accordance with that of hepcidin mRNA. Our data suggest that IL-6 may regulate hepcidin expression at the CP, upon interaction with the cognate cellular receptor, and through the Stat3 signaling transduction pathway.
Aging ; physiology ; Animals ; Choroid Plexus ; metabolism ; Hepcidins ; physiology ; Interleukin-6 ; physiology ; Iron ; metabolism ; RNA, Messenger ; Rats ; Rats, Inbred F344 ; STAT3 Transcription Factor ; physiology ; Signal Transduction

Genetic Therapy ; Hepatitis B ; therapy ; virology ; Hepatocytes ; cytology ; Humans ; Interleukin-6 ; genetics ; physiology ; Liver Regeneration ; drug effects ; Receptors, Interleukin-6 ; genetics ; physiology ; Recombinant Fusion Proteins ; genetics ; physiology ; Signal Transduction

OBJECTIVETo explore the biological effect of Notch ligand Delta-1 (Notch L delta-1) on the sIL-6R during the differentiation of erythroid hematopoiesis.

METHODSMononuclear cells (MNCs) was isolated from the normal cord blood using Ficoll graduation solution. MNCs were enriched for CD34(+) CD38(-) cells by CD34 immunomagnetic beads and a FACS Vantage. CD34(+) CD38(-) cells was cultured for 7 days in the presence of SCF, Flt3L, TPO and IL-3 (4GFs). The cultured cells was detected for the expression of IL-6R and GPA. The subsequently enriched CD36(+) erythroid progenitors were sorted for cells with IL-6R(+) and IL-6R(-) using FACS Vantage. The CD36(+) GPA(-) IL-6R(-) cells were respectively cultured in the 4GFs, 4GFs + IL-6 or 4GFs + FP6 containing medium in the presence or absence of Notch L delta-1 for 14 days and CD36(+) GPA high red cells were counted.

RESULTSIL-6R cells accounted for 95% of CD36(+) GPA(+) cells. The CD36(+) GPA(-) cells was clearly divided into IL-6R(+) (46%) and IL-6R(-) (54%) subpopulations, the IL-6R(+) cell subpopulation formed only a few GM colonies (2.1 +/- 1.8) and a greater number of BFU-E colonies were generated from the IL-6R(-) subpopulation (58.2 +/- 18.1) (P < 0.05). The number of CD36(+) GPA high cell was (1.400 +/- 0.180) x 10(6) in the presence of FP6, lower than that [(2.460 +/- 0.190) x 10(6)] in the presence of FP6 + Notch L delta-1 (P < 0.05).

CONCLUSIONNotch L delta-1 enhances the sIL-6R-mediated effects of IL-6 on the generation of erythroid cells.

ADP-ribosyl Cyclase 1 ; Antigens, CD34 ; Cell Differentiation ; drug effects ; physiology ; Cells, Cultured ; Erythroid Precursor Cells ; cytology ; drug effects ; Humans ; Interleukin-6 ; metabolism ; physiology ; Intracellular Signaling Peptides and Proteins ; Membrane Proteins ; pharmacology ; Receptors, Interleukin-6 ; metabolism ; physiology

The article reviewed the advance and the forensic meaning of macrophage on the wound age estimation during the wound healing process in resent years. It has also been summarized the relationship between macrophages and wound age estimation on the expression of cytokines derived from macrophages, the changes of macrophage phenotypes and the development process of phagosomes in macrophages after wounding. It is suggested that some regular and characteristic changes of macrophage should be a useful mark to wound age estimation and reminds therefore further study in this field.
Forensic Medicine ; Humans ; Interleukin-1/genetics* ; Interleukin-10/genetics* ; Interleukin-6/genetics* ; Macrophages/physiology* ; Phagosomes/physiology* ; Phenotype ; Time Factors ; Transforming Growth Factor beta/genetics* ; Tumor Necrosis Factor-alpha/genetics* ; Wound Healing/physiology*

BACKGROUNDThere is a higher rate of cytomegalovirus (CMV) reactivation in patients with multiple myeloma after an autologous stem cell transplantation, but no attention has been given thus far to a possible pathogenetic interplay between CMV and multiple myeloma. CMV can infect many kinds of cells, and CMV infection has been shown to inhibit apoptotic responses in several cell systems. In this study the authors investigated the alterations in apoptosis in the multiple myeloma cell line KM3 after infection with CMV and proposed a possible mechanism.

METHODSKM3 cells were infected with 100, 10, or 1 TCID50 of CMV and then cultured in serum-free RPMI 1640. An RT-PCR-based assay was used to detect mRNA expression of CMV-IE, glyceraldehyde-3-phosphate dehydrogenase (GAPDH), and IL-6 in CMV-infected and mock-infected cells. Flow cytometry was used to detect apoptotic cells. CMV particles and apoptotic cells were also examined with an electron microscope.

RESULTSCMV-infected KM3 cells clearly expressed immediate early (IE) antigen mRNA when compared to uninfected cells, and there were fewer apoptotic cells among cells treated with 100 or 10 TCID50 of CMV after culturing in serum-free RPMI 1640. CMV particles were observable in infected cells under an electron microscope. Expression of IL-6 mRNA increased after infection.

CONCLUSIONCMV can infect the multiple myeloma cell line KM3, inhibit the apoptotic response in these cells after apoptosis induction in serum-free culture, and increase the expression of IL-6 mRNA.

Apoptosis ; physiology ; Cell Line, Tumor ; Cytomegalovirus ; physiology ; Flow Cytometry ; Humans ; Immediate-Early Proteins ; analysis ; Interleukin-6 ; genetics ; physiology ; Multiple Myeloma ; pathology ; RNA, Messenger ; analysis ; Viral Proteins ; analysis