Modulatory effect of Tim-3/Galectin-9 axis on T-cell-mediated immunity in pulmonary tuberculosis

Patients affected by pulmonary tuberculosis (PTB) manifest deficiencies in innate cellular immunity. The Tim3/Galectin-9 axis is an important regulator of Th1 cell immunity, leading to Th1 cell apoptosis. Herein, thisstudy aims to clarify the underlying roles of the Tim-3/Galectin-9 axis in T-cell immunity in PTB. Peripheralblood mononuclear cells (PBMCs) were extracted from subjects with and without PTB to examine theexpression of CD4, CD8, CD25, and Tim-3 under the stimulation of Mycobacterium tuberculosis (MTB) andpurified protein derivative (PPD). In addition, the expression of Tim-3 and Galectin-9 in PBMCs was determined. The Tim-3/Galectin-9 axis in the PBMCs was activated or blocked to detect the secreted levels of IFNc, TNF-a, IL-2, and IL-22. MTB stimulation increased the expression of CD4, CD8, CD25, Tim-3, andGalectin-9 in PBMCs. The blockade of Tim-3/Galectin-9 axis resulted in reduced secretion of IFN-c, TNF-a,IL-2, and IL-22 from T-cells. Moreover, Tim-3?CD4?T, Tim-3?CD8?, and Tim-3?CD25?T cells exhibited agreater ability to inhibit the replication of MTB in macrophages. Taken conjointly, the blockade of Tim-3/Galectin-9 axis inhibits the secretion of inflammatory cytokines in T-cells to regulate the T-cell immunity inPTB.

Effect of ethyl pyruvate on renal high mobility group box-1 protein expression and acute kidney injury in rats with delayed resuscitation after thermal injury / 中华外科杂志

<p><b>OBJECTIVE</b>To investigate the effect of ethyl pyruvate (EP) on high mobility group box-1 protein (HMGB1) expression in renal tissue and acute kidney injury in rats with delayed resuscitation after thermal injury.</p><p><b>METHODS</b>Seventy-eight Wistar rats subjected to 30% total body surface area full-thickness thermal injury followed with delayed resuscitation were divided into 3 groups: sham group (n = 18), injury group (n = 30) and EP group (n = 30). Renal tissue and blood samples were harvested to determine HMGB1 mRNA as well as its protein expression and renal function parameter at the 8, 24, 72 h post the "injury". HMGB1 mRNA was semi-quantitatively measured by reverse transcription polymerase chain reaction taking GAPDH as an internal standard, and HMGB1 protein expression was determined by Western blot and immunohistochemistry. Blood urea nitrogen (BUN) levels were measured with automatic biochemistry analyzer. The pathological changes of renal tissues were examined using HE staining.</p><p><b>RESULTS</b>Compared with sham controls, both mRNA and protein expressions of HMGB1 in injury group were significantly enhanced in kidneys at 8 - 72 h after thermal injury (P < 0.05), meanwhile serum BUN levels were markedly increased (P < 0.05). Compared with injury group, the renal HMGB1 mRNA and protein expressions were markedly down-regulated in EP group at 8 h, 24 h and 72 h post injury (P < 0.05), respectively, and meanwhile serum BUN levels were reduced significantly (P < 0.05). Inflammatory cell infiltration was found in renal tissues following injury, and kidney injury was markedly alleviated after treatment with EP.</p><p><b>CONCLUSIONS</b>It indicated that HMGB1 appears to be involved in the pathogenesis of post-burn acute kidney injury. Treatment with EP reduces renal HMGB1 expression, and protects against acute kidney injury secondary to delayed resuscitation after major burns.</p>

Effect of Xuebijing injection on renal high mobility group box-1 protein expression and acute kidney injury in rats after scald injury / 中国医学科学院学报

<p><b>OBJECTIVE</b>To investigate the change in renal high mobility group box-1 protein (HMGB1) levels, and the effect of Chinese traditional medicine-Xuebijing injection on HMGB1 expression as well as acute kidney injury in rats after scald injury.</p><p><b>METHODS</b>Wistar rats were subjected to 30% full-thickness scald injury followed with delayed resuscitation. Totally 78 animals were divided into sham scald group (n=18), scald injury group (n=30), and Xuebijing injection treatment group (n=30). All animals were sacrificed at 8, 24, and 72 hours postburn. Renal tissue and blood samples were harvested to determine HMGB1 mRNA as well as protein expression and organ functional parameters. HMGB1 mRNA level was semi-quantitatively measured by the reverse transcription polymerase chain reaction taking GAPDH as an internal standard, and protein expressions of HMGB1 were detected by both Western blot and immunohistochemistry. Serum creatinine (Cr) contents were measured by automatic biochemistry analyzer. In addition, pathological lesions in kidney were observed under light microscope using HE staining.</p><p><b>RESULTS</b>Compared with sham scald group, both mRNA and protein expressions of HMGB1 were significantly enhanced in the kidney at 8, 24, and 72 hours after scald injury (P<0.05, P<0.01), meanwhile serum Cr contents were markedly increased following acute insults (P<0.05, P<0.01). Treatment with Xuebijing injection could markedly down-regulated renal HMGB1 mRNA expression and protein release at 24 hours and 72 hours (P<0.05, P<0.01), and significantly reduced serum Cr content following scald injury (P<0.05). Many inflammatory cells in renal tissues were observed using light microscope following scald. The histological morphology of kidney lesions was a-HMGB1, a late mediator, appears to be inmeliorated after treatment with Xuebijing injection.</p><p><b>CONCLUSIONS</b>volved in the pathogenesis of excessive inflammatory response and acute kidney damage. Treatment with Xuebijing injection can inhibit HMGB1 synthesis and release in renal tissues, and may prevent the development of acute kidney injury induced by serious scald injury.</p>

The potential mechanism on signal transduction pathway in regulation of mRNA expression of high mobility group box-1 protein in septic rats / 中华外科杂志

<p><b>OBJECTIVE</b>To investigate the potential role of Janus kinase/signal transducer and activator of transcription (JAK/STAT) pathway in regulation of gene expression of high mobility group box-1 protein (HMGB1) in various tissues in rats with sepsis.</p><p><b>METHODS</b>A sepsis model reproduced by cecal ligation and puncture (CLP), and 128 male Wistar rats were randomly divided into normal control group (n = 10), sham operation group (n = 10), CLP group (n = 60), AG490 treatment group (n = 24), and rapamycin (RPM) treatment group (n = 24). At serial time points animals in each group were sacrificed after CLP, then tissue samples were harvested to determine HMGB1 mRNA expression and STAT1/3 DNA binding activity.</p><p><b>RESULTS</b>STAT1 activities increased rapidly in the liver, lungs and small intestine after CLP, peaking at 6 - 12 h, while it increased slowly, and still kept at mild level from 2 to 48 h in the kidneys. Compared with STAT1, lower STAT3 activities were detected only in the liver and lungs, with negative detection in the small intestine and kidneys. HMGB1 mRNA levels significantly increased in liver, lungs and small intestine at various time points after CLP respectively (P < 0.05 or P < 0.01), while they didn't change in the kidneys. Treatment with AG490 could markedly inhibit HMGB1 mRNA expression in the liver and small intestine at 24 and 48 h (P < 0.05 or P < 0.01), and in lungs at 2 h following CLP (P < 0.01). Similarly, treatment with RPM significantly decreased HMGB1 mRNA expression in the lungs at 2, 6, 24 and 48 h, in the liver at 6 and 24 h, and in the small intestine at 24 and 48 h (P < 0.05 or P < 0.01). In addition, STAT1 and STAT3 activities in the liver and lungs were significantly correlated with corresponding tissue HMGB1 mRNA expression.</p><p><b>CONCLUSIONS</b>Peritoneal infection could extensively activate STAT1 and limitedly activate STAT3 in vital organs. Activation of JAK/STAT pathway might be involved in up-regulating the gene expression of HMGB1 and systemic inflammation secondary to severe septic challenge.</p>