Showing papers by "Anoop Kumar published in 2013"
TL;DR: Results define a novel mechanism by which probiotics counteract PAF-induced inflammation in IECs, and suggest that soluble factor(s) in the CS of LA mediate these effects.
Abstract: Probiotics have been used as alternative prevention and therapy modalities in intestinal inflammatory disorders including inflammatory bowel diseases (IBD) and necrotizing enterocolitis (NEC). Pathophysiology of IBD and NEC includes the production of diverse lipid mediators, including platelet-activating factor (PAF) that mediate inflammatory responses in the disease. PAF is known to activate NF-κB, however, the mechanisms of PAF-induced inflammation are not fully defined. We have recently described a novel PAF-triggered pathway of NF-κB activation and IL-8 production in intestinal epithelial cells (IECs), requiring the pivotal role of the adaptor protein Bcl10 and its interactions with CARMA3 and MALT1. The current studies examined the potential role of the probiotic Lactobacillus acidophilus in reversing the PAF-induced, Bcl10-dependent NF-κB activation and IL-8 production in IECs. PAF treatment (5 µM×24 h) of NCM460 and Caco-2 cells significantly increased nuclear p65 NF-κB levels and IL-8 secretion (2-3-fold, P<0.05), compared to control, which were blocked by pretreatment of the cells for 6 h with L. acidophilus (LA) or its culture supernatant (CS), followed by continued treatments with PAF for 24 h. LA-CS also attenuated PAF-induced increase in Bcl10 mRNA and protein levels and Bcl10 promoter activity. LA-CS did not alter PAF-induced interaction of Bcl10 with CARMA3, but attenuated Bcl10 interaction with MALT1 and also PAF-induced ubiquitination of IKKγ. Efficacy of bacteria-free CS of LA in counteracting PAF-induced inflammatory cascade suggests that soluble factor(s) in the CS of LA mediate these effects. These results define a novel mechanism by which probiotics counteract PAF-induced inflammation in IECs.
40 citations
TL;DR: A novel role of HDAC2 is identified as a regulator of SERT gene expression in intestinal epithelial cells and mechanisms involving histone hyperacetylation may be involved.
Abstract: The serotonin (5-HT) transporter (SERT) facilitates clearance of extracellular 5-HT by its uptake and internalization. Decreased expression of SERT and consequent high 5-HT levels have been implica...
33 citations
TL;DR: The findings define the posttranslational and transcriptional mechanisms underlying stimulation of Pgp function and expression by KGF2 that may contribute to the beneficial effects of K GF2 in intestinal inflammatory disorders.
Abstract: Intestinal P-glycoprotein (Pgp/multidrug resistance 1), encoded by the ATP-binding cassette B1 gene, is primarily involved in the transepithelial efflux of toxic metabolites and xenobiotics from th...
13 citations
TL;DR: The data indicate that the acid-dependent NHE2 stimulation is implemented by transcriptional upregulation of NHE1-3 via acid-induced Egr-1 in the intestinal epithelial cells.
Abstract: Na+/H+ exchangers (NHEs) play important roles in regulating internal pH (pHi), cell volume and neutral Na+ absorption in the human intestine. Earlier studies have shown that low extracellular pH (pHe) and metabolic acidosis increases the expression and function of NHE1-3 genes. However, transcriptional mechanisms involved remained unknown. Therefore, we investigated the molecular mechanisms underlying acid-induced NHE2 expression in C2BBe1 and SK-CO15 intestinal epithelial cells. Assessing total RNA and protein by RT-PCR and Western blot analysis, respectively, displayed significant increases in the NHE2 mRNA and protein levels in cells exposed to acidic media (pH 6.5 and 6.7) compared to normal medium. Acid treatment was also associated with a significant enhancement in NHE2 transport activity. Quantification of the heterogeneous nuclear RNA indicated that the rate of NHE2 transcription was increased in response to acid. Furthermore, acid caused a significant increase in NHE2 promoter activity confirming transcriptional upregulation. Through functional and mutational studies the acid-response element was mapped to a 15-nucleotide GC-rich sequence at bp −337 to −323 upstream from the transcription start site. We previously identified this element as an overlapping Egr-1/Sp1/Egr-1 motif that was essential for the NHE2 upregulation by mitogen-induced transcription factor Egr-1. Cells exposed to acid exhibited a temporal increase in Egr-1 mRNA and protein expression. These events were followed by Egr-1 nuclear accumulation, as detected by immunofluorescence microscopy, and potentiated its in vitro and in vivo interaction with the NHE2 promoter. Disruption of ESE motif and knockdown of Egr-1 expression by targeted small interfering RNA abrogated the acid-induced NHE2 transcriptional activity. These data indicate that the acid-dependent NHE2 stimulation is implemented by transcriptional upregulation of NHE2 via acid-induced Egr-1 in the intestinal epithelial cells.
6 citations
TL;DR: The definition of industry under section 2(j) of the IDA was considered by the Supreme Court in the land mark judgment of Bangalore Water Supply and Sewerage Board Vs A.Rajjapa and Ors 1, wherein the court laid down the broad interpretation of the term industry as discussed by the authors.
Abstract: The term industry has always been a very controversial point in the area of industrial jurisprudence. However, there have been some judgments in a string of cases, which have tried to resolve the dispute and lay down an adequate definition whenever question arose. Later it has been realized that these definitions have created huge confusion. To pacify the situation the definition of industry under section 2(j) of the IDA was considered by the Supreme Court in the land mark judgment of Bangalore Water Supply and Sewerage Board Vs A.Rajjapa and Ors 1 , wherein the court laid down the broad interpretation of the term industry. This judgment holds importance because it was for the first time that a comparatively clear definition of the term was given. The phrases labour laws' and 'industrial laws' are used synonymously and refer to those laws and legal rules which regulate the employer-employee relations. Some of these laws impose certain obligations or confer certain rights upon the employers or the employees so that in the ultimate analysis they can be deemed to impinge upon employer-employee relations.