Modulation of signal transduction pathways in lymphocytes due to sub-lethal toxicity of chlorinated phenol.
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.
Limaye
Amita
A
National Centre for Cell Science, NCCS Complex, University of Pune Campus, Ganeshkhind, Pune, India.
Kashyap
Rajpal S
RS
Kapley
Atya
A
Galande
Sanjeev
S
Purohit
Hemant J
HJ
Daginawala
Hatim F
HF
Taori
Giridhar M
GM
D017209:Apoptosis / Q000187:drug effects; D049109:Cell Proliferation / Q000187:drug effects; D002470:Cell Survival / Q000187:drug effects; D002478:Cells, Cultured; D002733:Chlorophenols / Q000633:toxicity*; D004785:Environmental Pollutants / Q000633:toxicity*; D015870:Gene Expression / Q000187:drug effects; D006801:Humans; D016906:Interleukin-9 / Q000378:metabolism; D007378:Interleukins / Q000378:metabolism; D007963:Leukocytes, Mononuclear / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology; D020411:Oligonucleotide Array Sequence Analysis; D010416:Pentachlorophenol / Q000633:toxicity; D015398:Signal Transduction / Q000187:drug effects*; D014475:Uncoupling Agents / Q000633:toxicity*; D000098546:Interleukin-21
D002733:Chlorophenols; D004785:Environmental Pollutants; D016906:Interleukin-9; D007378:Interleukins; D014475:Uncoupling Agents; C056693:2,3,5-trichlorophenol; D010416:Pentachlorophenol; D000098546:Interleukin-21; C004762:2,4-dichlorophenol; C030682:3-chlorophenol