Modulation of signal transduction pathways in lymphocytes due to sub-lethal toxicity of chlorinated phenol.

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Limaye A, Kashyap RS, Kapley A, Galande S, Purohit HJ, Daginawala HF, Taori GM

Modulation of signal transduction pathways in lymphocytes due to sub-lethal toxicity of chlorinated phenol.

Toxicol Lett. 2008 Jun 10;179(1):23-8. doi: 10.1016/j.toxlet.2008.03.016. Epub 2008 Apr 8.

PubMed ID

18486366 [ View in PubMed

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Abstract

Chlorophenols and their derivatives are a major component of environmental pollutants that are potential immunotoxicants. Deaminase assay performed on peripheral blood mononuclear cells (PBMCs) exposed to chlorophenolic compounds and its derivatives demonstrated a decreased proliferation rate and cell death. Chlorophenolic exposure also led to impaired production of IL-21 and IL-9 along with many other cytokines and chemokines that potentiate the inflammatory response. Using the PBMC activation model and gene expression profiling we provide insights into mechanisms by which the chlorophenolic compounds and their derivatives, especially pentachlorophenol (PCP) dysregulate the inflammatory response. We have shown here that PCP represses IL21 and IL9 expression thus affecting various downstream signaling pathways. We propose that PCP, a potent pollutant, imparts its cytotoxicity by evading the immune response by simultaneously affecting multiple signaling pathways in lymphocytes.

DrugBank Data that Cites this Article

Pharmaco-transcriptomics

Drug	Drug Groups	Gene	Gene ID	Change	Interaction	Chromosome
3-Chlorophenol	Experimental	CCL11	6356	upregulated	3-chlorophenol results in increased expression of CCL11 mRNA	17q12
3-Chlorophenol	Experimental	CCL20	6364	upregulated	3-chlorophenol results in increased expression of CCL20 mRNA	2q36.3
3-Chlorophenol	Experimental	CCR2	729230	upregulated	3-chlorophenol results in increased expression of CCR2 mRNA	3p21.31
3-Chlorophenol	Experimental	CCR5	1234	downregulated	3-chlorophenol results in decreased expression of CCR5 mRNA	3p21.31
3-Chlorophenol	Experimental	IFNG	3458	upregulated	3-chlorophenol results in increased expression of IFNG mRNA	12q15
3-Chlorophenol	Experimental	IL21	59067	upregulated	3-chlorophenol results in increased expression of IL21 mRNA	4q27
3-Chlorophenol	Experimental	IL9	3578	upregulated	3-chlorophenol results in increased expression of IL9 mRNA	5q31.1
3-Chlorophenol	Experimental	UGT1A10	54575	upregulated	3-chlorophenol results in increased expression of UGT1A10 mRNA	2q37.1
3-Chlorophenol	Experimental	XCL2	6846	upregulated	3-chlorophenol results in increased expression of XCL2 mRNA	1q24.2
3-Chlorophenol	Experimental	XRCC4	7518	upregulated	3-chlorophenol results in increased expression of XRCC4 mRNA	5q14.2