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Salmonella enterica Typhimurium SipA induces CXC-chemokine expression through p38MAPK and JUN pathways.

Department of Veterinary Pathobiology, College of Veterinary Medicine and Biomedical Sciences, Texas A&M University, College Station, TX 77843-4467, USA.
Microbes and Infection (Impact Factor: 2.73). 02/2009; 11(2):302-10. DOI: 10.1016/j.micinf.2008.12.005
Source: PubMed

ABSTRACT The role of Salmonella typhimurium type III secretion system (T3SS-1)-translocated proteins in chemokines' expression and protein phosphorylation was investigated in HeLa cells. Infection of HeLa cells with S. typhimurium activated IL-8 and GRO-alpha expression at higher levels than infection with a S. typhimurium sipAsopABDE2 mutant, confirming that T3SS-1-secreted proteins are required to fully induce chemokine expression in HeLa cells. A S. typhimurium sipAsopABDE2 mutant complemented with sipA or a strain carrying a chromosomal copy of sipA (sopABDE2 mutant) activated chemokines at significantly higher levels than a S. typhimurium sipAsopABDE2 mutant. However, extracellular addition of recombinant SipA failed to induce IL-8 expression. Phosphorylation analyses revealed that S. typhimurium induced a twofold increase in the phosphorylation of B23, CREB1, ERK1, JUN, p38MAPK, and NR1. JUN and p38MAPK were phosphorylated by S. typhimurium carrying a chromosomal copy of sipA (sopABDE2 mutant) while none was more than twofold phosphorylated in cells infected with the S. typhimurium sipAsopABDE2 mutant. Treating cells with JUN and p38MAPK inhibitors significantly decreased IL-8 expression in sopABDE2 mutant infected cells. These data indicate that S. typhimurium SipA induces expression of CXC chemokines through phosphorylation of IL-8-transcription regulatory proteins, JUN and p38MAK.

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    • "How exactly SopB acts at this stage of the pathway was not determined. It has been reported that SopB affects the production of the cytokines that cause inflammation of the gut, a characteristic of Salmonella infection.7,60,61,62 Further studies are required to test whether SopB also plays a role in the secretion process. "
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    • "Efficient expression of SipA at late stage of infection in macrophages and in the spleen, as shown in our results, has been observed in Salmonella enterica serovar Typhimurium [15,16]. This is consistent with its functions in modulating actin dynamics and bacterial localization in infected macrophages [42-44] and in inducing inflammatory response for supporting Salmonella infection [45,46]. "
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    • "To correlate cytosolic calcium changes with IL-8 expression, bacterial internalization, and effector proteins, we used HeLa S3 cells, in which, as opposed to T84 cells, different profiles of responses to infection of S. Typhimurium wild type and mutant can be detected [23], therefore, questions related to specific effector proteins can be addressed. HeLa S3 cells (human cervical epithelial cells e ATCC) were grown in Kaighn's modification of Ham's F12 medium with 2 mM L-glutamine and 1.5 g/L sodium bicarbonate and supplemented with 10% fetal bovine serum. "
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