Molecular immunology
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Molecular immunology · Oct 2013
LetterA polymorphism in IL4 may associate with sensory neuropathy in African HIV patients.
Animal and in vitro models of HIV-associated sensory neuropathy suggest an inflammatory etiology. Previous genetic association studies of HIV-SN have been in small Caucasian or Asian cohorts. We assessed cytokine single nucleotide polymorphisms (SNPs) in a Black Southern African cohort. ⋯ We identified a novel association between IL4-590*T and HIV-SN in African HIV-positive patients which warrants further investigation.
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Molecular immunology · Jul 2013
Preventive and therapeutic oral administration of the pentacyclic triterpene α,β-amyrin ameliorates dextran sulfate sodium-induced colitis in mice: the relevance of cannabinoid system.
The pentacyclic triterpene α,β-amyrin has been previously reported as an effective compound in the treatment of several inflammatory conditions. Recent evidence indicates that α,β-amyrin displayed its effects through interaction with the cannabinoid pathway. We assessed the anti-inflammatory effects of the α,β-amyrin in the dextran sulfate sodium (DSS)-induced colitis in mice and investigated whether its effects were associated with the interaction with the cannabinoid system. ⋯ Interestingly, our results also showed that the cannabinoid receptor 1 (CB(1)), but not CB(2), pharmacological blockade significantly reversed the beneficial effects of α,β-amyrin in DSS-induced colitis. Besides, our data demonstrated that mRNA expression for both the endocannabinoid hydrolase monoglyceride lipase 1 (MGL1) and fatty acid amide hydrolase (FAAH) were significantly reduced in the colon of α,β-amyrin-treated mice. Altogether, these results suggest that the α,β-amyrin might possess potential therapeutic interest for the treatment of IBD, and also provide new insights for the underlying mechanisms.
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Molecular immunology · Oct 2012
Complement activation and toll-like receptor-2 signaling contribute to cytokine production after renal ischemia/reperfusion.
The innate immune system causes tissue inflammation and injury after renal ischemia/reperfusion (I/R). The complement system is activated on ischemic tubular epithelial cells (TECs) and induces the cells to produce pro-inflammatory chemokines. TECs also express toll-like receptors (TLRs)-2 and -4. ⋯ To test this hypothesis we induced ischemic acute kidney injury (AKI) in wild-type mice, mice with targeted deletion of complement factor B (fB(-/-) mice), or mice with targeted deletion of factor B and TLR-2 (fB(-/-)TLR2(-/-) mice). Surprisingly, we found that fB(-/-)TLR2(-/-) mice developed more severe injury than those with single deficiency of factor B. Our results indicate that blockade of the complement system may be more protective than simultaneous blockade of both the complement system and TLR-2 in ischemic AKI.
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Molecular immunology · Aug 2012
Glycogen synthase kinase-3 beta inhibitor suppresses Porphyromonas gingivalis lipopolysaccharide-induced CD40 expression by inhibiting nuclear factor-kappa B activation in mouse osteoblasts.
Bone-forming osteoblasts have been recently reported capable of expressing the critical co-stimulatory molecule CD40 upon exposure to bacterial infection, which supports the unappreciated role of osteoblasts in modulating bone inflammation. Recent studies highlight the anti-inflammatory potential of glycogen synthase kinase-3β (GSK-3β) inhibitors; however, their effect on osteoblasts remains largely unclear. In the present study, we showed that treatment with SB216763, a highly specific GSK-3β inhibitor, resulted in a dose-dependent decrease in the mRNA and protein expression of CD40, as well as production of pro-inflammatory cytokines IL-6, TNF-α and IL-1β, in the Porphyromonas gingivalis-lipopolysaccharide (LPS)-stimulated murine osteoblastic-like MC3T3-E1 cells. ⋯ Closer investigation by immunoprecipitation assay revealed that β-catenin can physically interact with NF-κBp65. The negative regulation effect of GSK-3β inhibitor on CD40 expression is mediated through β-catenin, for siRNA of β-catenin attenuated the GSK-3β inhibitor-induced repression of NF-κB activation and, consequently, the expression of CD40 and production of pro-inflammatory cytokines in LPS-stimulated MC3T3-E1 cells. Thus our results elucidate the molecular mechanisms whereby GSK-3β inhibitor prevents the LPS-induced CD40 expression on osteoblasts and provide supportive evidence of the potential role of GSK-3β inhibitors in suppressing the immune function of osteoblasts in inflammatory bone diseases.
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Molecular immunology · Jul 2012
mGluR1 interacts with cystic fibrosis transmembrane conductance regulator and modulates the secretion of IL-10 in cystic fibrosis peripheral lymphocytes.
Cystic fibrosis (CF) is caused by the mutations in the gene encoding the cystic fibrosis transmembrane conductance regulator (CFTR) chloride channel. CFTR dysfunction in T cells could lead directly to aberrant immune responses. The action of glutamate on the secretion of IL-8 and IL-10 by lymphocytes derived from healthy subjects and cystic CF patients, as well as the expression of metabotropic glutamate receptor subtype 1 (mGluR1) in the membrane fractions of lymphocytes was investigated. ⋯ We have found that normal, non-mutated CFTR, as well as mutated forms of CFTR were associated with metabotropic mGluR1, but the level of surface exposed mGluR1 in CF-lymphocytes was much lower than in normal cells. Besides, our results have shown that normal, non-mutated CFTR, as well as mutated forms of CFTR were associated with NHERF-1 and CAL; however in lymphocytes with CFTR mutation the amount of cell-surface expressed CFTR-CAL complex was greatly decreased. We have concluded that CFTR and mGluR1 could compete for binding to CAL, which in turn downregulates the post-synthetic trafficking of mGluR1 and decreases the synthesis of IL-10.