The pattern of metabolism changes obviously after severe burn trauma, and it is characterized by an immensely increase in energy consumption, persistent strengthening in catabolism, and impediment of utilization of nutrient substrate. It will lead to autophagy, continuous consumption, and progressive emaciation, etc. If these pathological phenomena can not be effectively corrected, the prognosis of patients with serious burn will be poor, with complications of organ damage, immune dysfunction, and delayed wound healing, etc. Hypermetabolism after burn has become one of the leading causes of multiple organ dysfunction and even death. After many years' research, we have a certain understanding of burn hypermetabolism, but it is still difficult to clearly explain the mechanism up to now. Moreover, the measures of regulating hypermetabolism are still not perfect, hampering the advance of treatment of serious burn trauma. The purpose of the article is to analyze and discuss the essential mechanism of hypermetabolism after burn, basing on the new literature and a series of our experimental and clinical studies. Meanwhile the regulation strategy concerning burn hypermetabolism is proposed. It focuses on regulation of endocrine and inflammatory mediators, as well as maintenance of gastrointestinal structure and function.
Burns ; metabolism ; pathology ; therapy ; Endocrine System ; Gastrointestinal Tract ; Humans ; Inflammation ; Inflammation Mediators

Animals ; Inflammation Mediators/metabolism* ; Macrophages/metabolism* ; Mice ; Stromal Interaction Molecule 1/metabolism*

OBJECTIVE: To investigate the role of acetylated modification induced by coactivator p300 in lipopolysaccharide (LPS)- induced inflammatory mediator synthesis and its molecular mechanism. METHODS: Agilent SurePrint G3 Mouse Gene Expression V2 microarray chip and Western blotting were used to screen the molecules whose expression levels in mouse macrophages (RAW246.7) were correlated with the stimulation intensity of LPS. Electrophoretic mobility shift assay (EMSA) and chromatin immunoprecipitation (chip-qPCR) were used to verify the binding of the molecules to the promoters of IL-6 and TNF-α genes. The effects of transfection of RAW246.7 cells with overexpression or interfering plasmids on IL-6 and TNF-α synthesis were evaluated with ELISA, and the binding level of the target molecules and acetylation level of H3K27 in the promoter region of IL-6 and TNF-α genes were analyzed by chromatin immunoprecipitation sequencing technique (chip-seq). RESULTS: Gene microarray chip data and Western blotting both confirmed a strong correlation of p300 expression with the stimulation intensity of LPS. Immunocoprecipitation confirmed the binding between p300 and c-myb. The results of EMSA demonstrated that c-myb (P < 0.05), but not p300, could directly bind to the promoter region of IL-6 and TNF-α genes; p300 could bind to the promoters only in the presence of c-myb (P < 0.05). The expressions of p65, p300 and c-myb did not show interactions. Both p300 overexpression and LPS stimulation could increase the level of promoter-binding p300 and H3K27 acetylation level, thus promoting p65 binding and inflammatory gene transcription; such effects were obviously suppressed by interference of c-myb expression (P < 0.05). Interference of p65 resulted in inhibition of p65 binding to the promoters and gene transcription (P < 0.05) without affecting p300 binding or H3K27 acetylation level. CONCLUSION LPS can stimulate the synthesis of p300, whose binding to the promoter region of inflammatory genes via c-myb facilitates the cohesion of p65 by inducing H3K27 acetylation, thus promoting the expression of the inflammatory genes.
Acetylation ; Animals ; Inflammation Mediators ; Interleukin-6/metabolism* ; Lipopolysaccharides/pharmacology* ; Mice ; Tumor Necrosis Factor-alpha/metabolism*

The temperature-sensitive transient receptor potential (TRP) channels, is also called thermo TRP, including TRPV1, TRPV2, TRPV3, TRPV4, TRPM8 and TRPA1, which are expressed in sensory neurons and non-neuronal cells (e.g.keratinocyte, mast cell) of the skin. Thermo TRP channels are activated/sensitized by physical and chemical mediators, which participate in thermosensation and thermoregulation, so that they are key players in pruritus or pain pathogenesis. Thermo TRP channels are also involved in cutaneous neurogenic inflammation, thus they are regarded as molecular targets for future therapy in skin inflammation, pruritus and pain. In addition, following a basic syntax and molecular substrate of nociception and pruriception established by TRP channels-centered concept, the sensory categories can be distinguished and re-defined. Thermo TRP channels should be taken into account when analyzing the pathogenesis and management of itch or pruritic dermatosis.
Humans ; Inflammation ; metabolism ; physiopathology ; Inflammation Mediators ; physiology ; Pruritus ; metabolism ; Sensory Receptor Cells ; metabolism ; Skin ; innervation ; metabolism ; Thermoreceptors ; metabolism ; Transient Receptor Potential Channels ; metabolism ; physiology

Asthma ; drug therapy ; metabolism ; Cytokines ; metabolism ; Drugs, Chinese Herbal ; pharmacology ; therapeutic use ; Humans ; Inflammation Mediators ; metabolism ; Phytotherapy ; Signal Transduction

It has become increasingly clear that cytokines play an important role in modulating neuroendocrine regulation, especially in the secretion of corticotropin (ACTH) in the pituitary. Oncostatin M (OSM), a cytokine of IL-6 family has been reported to increase ACTH secretion and pro-opiomelanocortin (POMC) transcription in murine corticotroph pituitary tumor cells (AtT20 cells). The present study was undertaken to determine the effects of OSM on hormonal release in primary culture of rat pituitary cells. Growth hormone or prolactin release was not affected by OSM. OSM (1 nM) stimulated ACTH release (35.1% increase versus control, p>0.001) in dispersed pituitary cells of rat to a lesser extent than in AtT20 cells. Corticotropin releasing hormone (CRH) (10 nM) also induced a 2.3-fold increase of ACTH secretion (p>0.001), but co-treatment of OSM and CRH did not exhibit any synergistic effect on ACTH secretion. We conclude OSM has a stimulatory effect on ACTH secretion in normal rat pituitary cell cultures, and OSM acts mainly on corticotroph, supporting the potential role of OSM to modulate immune-endocrine regulation in the pituitary.
Animal ; Cells, Cultured ; Corticotropin/secretion* ; Cytokines/pharmacology ; Cytokines/metabolism* ; Inflammation Mediators/pharmacology ; Inflammation Mediators/metabolism* ; Male ; Peptides/pharmacology ; Peptides/metabolism* ; Pituitary Gland/metabolism* ; Pituitary Gland/drug effects ; Pituitary Gland/cytology ; Prolactin/secretion* ; Rats ; Rats, Inbred WF ; Somatotropin/secretion*

It has become increasingly clear that cytokines play an important role in modulating neuroendocrine regulation, especially in the secretion of corticotropin (ACTH) in the pituitary. Oncostatin M (OSM), a cytokine of IL-6 family has been reported to increase ACTH secretion and pro-opiomelanocortin (POMC) transcription in murine corticotroph pituitary tumor cells (AtT20 cells). The present study was undertaken to determine the effects of OSM on hormonal release in primary culture of rat pituitary cells. Growth hormone or prolactin release was not affected by OSM. OSM (1 nM) stimulated ACTH release (35.1% increase versus control, p>0.001) in dispersed pituitary cells of rat to a lesser extent than in AtT20 cells. Corticotropin releasing hormone (CRH) (10 nM) also induced a 2.3-fold increase of ACTH secretion (p>0.001), but co-treatment of OSM and CRH did not exhibit any synergistic effect on ACTH secretion. We conclude OSM has a stimulatory effect on ACTH secretion in normal rat pituitary cell cultures, and OSM acts mainly on corticotroph, supporting the potential role of OSM to modulate immune-endocrine regulation in the pituitary.
Animal ; Cells, Cultured ; Corticotropin/secretion* ; Cytokines/pharmacology ; Cytokines/metabolism* ; Inflammation Mediators/pharmacology ; Inflammation Mediators/metabolism* ; Male ; Peptides/pharmacology ; Peptides/metabolism* ; Pituitary Gland/metabolism* ; Pituitary Gland/drug effects ; Pituitary Gland/cytology ; Prolactin/secretion* ; Rats ; Rats, Inbred WF ; Somatotropin/secretion*

OBJECTIVETo investigate the effect of oleic acid on the proliferation and secretion of pro-inflammatory mediators of human normal fibroblasts and scar fibroblasts.

METHODSHuman normal fibroblasts and scar fibroblasts were cultured in vitro and respectively divided into seven groups according to the random number table, with 8 samples in each group. Cells in blank control (BC) group were routinely cultured without addition of other agents. Cells in ethanol-control (EC) group were cultured with medium with the addition of 2% absolute ethanol. Cells in oleic acid groups were cultured with the addition of oleic acid in concentration of 0.25, 0.50, 1.00, 2.00, or 4.00 mmol/L in 2% absolute ethanol. The growth of cells in each group was observed with trypan blue staining on post culture day (PCD) 1-5. On PCD 2, structure of cells in BC, EC, and 1.00 mmol/L oleic acid groups was observed under inverted phase contrast microscope and transmission electron microscope; cell cycle of BC, EC, and 1.00 mmol/L oleic acid groups was measured by flow cytometer; cell proliferation activity in each group was measured by MTT assay; the level of NO in supernatant was assayed by Griess assay; the levels of TNF-α, IL-1β, IL-6, and IL-8 in supernatants in each group were determined by enzyme-linked immunosorbent assay. Data were processed with multifactor and repeated measurement design analysis of variance.

RESULTS(1) There was no significant difference in each index of normal fibroblasts and scar fibroblasts between BC group and EC group. (2) The numbers of normal fibroblasts and scar fibroblasts in 2.00 and 4.00 mmol/L oleic acid groups were significantly lower than those in corresponding BC and EC groups on PCD 2-5 (with F values respectively 13.773 and 11.344, P values all below 0.01). (3) On PCD 2, the numbers of normal fibroblasts and scar fibroblasts in 1.00 mmol/L oleic acid groups decreased, and the cells were aggregating, rounding, and easy to drop off. Cellular membrane disruption, vacuolar degeneration of mitochondrion, pyknosis, and lipid droplets were observed. (4) The percentages of G0/G1 and G2/M phases of normal fibroblasts in 1.00 mmol/L oleic acid group [(93.56 ± 9.98)%, (2.01 ± 0.75)%] were significantly higher than those in BC group [(84.23 ± 10.96)%, (0.37 ± 0.16)%, with F values respectively 3.026, 34.751, P < 0.05 or P < 0.01], while the percentage of normal fibroblasts in S phase [(4.42 ± 0.87)%] was markedly lower than that in BC group [(16.06 ± 1.74)%, F = 136.120, P < 0.01]. The percentages of scar fibroblasts of G0/G1 and G2/M phases in 1.00 mmol/L oleic acid group [(93.86 ± 13.90)%, (1.89 ± 0.66)%] were significantly higher than those in BC group [(83.88 ± 10.42)%, (0.41 ± 0.17)%, with F values respectively 3.529, 32.710, P < 0.05 or P < 0.01], and the percentage of scar fibroblasts in S phase [(3.87 ± 0.63)%] was markedly lower than that in BC group [(15.89 ± 2.02)%, F = 116.508, P < 0.01]. (5) The proliferation rates of normal fibroblasts and scar fibroblasts in 0.50-4.00 mmol/L oleic acid groups were significantly lower than those in corresponding BC and EC groups (with F values respectively 215.945 and 194.555, P < 0.05 or P < 0.01). (6) The content of NO in supernatant of normal fibroblasts in all oleic acid groups was obviously higher than that in BC and EC groups (F = 30.240, P < 0.05 or P < 0.01). The contents of NO in supernatants of scar fibroblasts in 1.00-4.00 mmol/L oleic acid groups were significantly higher than that in BC and EC groups (F = 12.495, P < 0.01). The contents of TNF-α and IL-6 in supernatants of normal fibroblasts and scar fibroblasts in 2.00 and 4.00 mmol/L oleic acid groups were obviously higher than those in corresponding BC and EC groups (with F(TNF-α) values respectively 6.911, 3.818, F(IL-6) values respectively 16.939, 11.600,P < 0.05 or P < 0.01). The contents of IL-1β in supernatants of normal fibroblasts and scar fibroblasts in groups of every concentration of oleic acid were significantly higher than those in corresponding BC and EC groups (with F values respectively 25.117, 9.137, P values all below 0.01). The contents of IL-8 in supernatants of normal fibroblasts in 1.00-4.00 mmol/L oleic acid groups were markedly higher than those in BC and EC groups (F = 2.717, P < 0.05 or P < 0.01). The contents of IL-8 in supernatants of scar fibroblasts in 2.00 and 4.00 mmol/L oleic acid groups were significantly higher than those in BC and EC groups (F = 3.338, P < 0.05). There was no statistically significant difference in above indexes between normal fibroblasts and scar fibroblasts in the same concentration of oleic acid group (with F values from 0.120 to 3.766, P values all above 0.05).

CONCLUSIONSAlthough oleic acid in high concentration inhibits the proliferation of scar fibroblasts, it also inhibits the proliferation of normal fibroblasts. Oleic acid in high concentration can cause excessive and continued inflammatory reaction by promoting the secretion of pro-inflammatory mediators of normal fibroblasts and scar fibroblasts, and they are detrimental to wound healing.

Cell Proliferation ; drug effects ; Cells, Cultured ; Cicatrix ; metabolism ; Fibroblasts ; cytology ; drug effects ; secretion ; Humans ; Inflammation Mediators ; metabolism ; Oleic Acid ; pharmacology

Acute Disease ; Adult ; Altitude Sickness ; blood ; pathology ; Bronchoalveolar Lavage Fluid ; chemistry ; Case-Control Studies ; Humans ; Inflammation Mediators ; metabolism ; Male

OBJECTIVETo investigate the effect of angiotensin II (AngII) type 2 (AT2) receptors on pressure overload-induced inflammatory cytokine secretion in adult rat hypertrophied cadiomyocytes.

METHODSRat models of left ventricular hypertrophy induced by pressure overload was established by placing a band around the abdominal aortic of the rats, from which the hypertrophied cadiomyocytes were isolated and purified 8 weeks later. The isolated cardiomyocytes were treated with AngII plus losartan or AngII plus PD123319, and 36 h after the treatments, the expression levels of tumor necrosis factor-alpha (TNF-alpha), interleukin-1beta (IL-1beta) and IL-6 in the supernatant were detected using radioimmunoassay.

RESULTSAngII induced TNF-alpha and IL-1beta secretion from the hypertrophied cardiomyocyets, and pretreatment of the cells with PD123319, but not losartan, decreased their secretion. IL-6 level was not detected in the supernatant.

CONCLUSIONAngII-induced the expression of inflammatory cytokines in adult rat hypertrophied cardiomyocytes is mediated mainly by AT2, not by AT1 receptors.

Animals ; Cells, Cultured ; Cytokines ; secretion ; Hypertrophy ; metabolism ; pathology ; Inflammation Mediators ; metabolism ; Myocytes, Cardiac ; metabolism ; pathology ; Rats ; Rats, Sprague-Dawley ; Receptor, Angiotensin, Type 2 ; metabolism