Targeting apoptotic signalling pathway and pro-inflammatory cytokine expression as therapeutic intervention in TPE induced lung damage.
Tropical pulmonary eosinophilia (TPE) is an occult manifestation of filariasis, brought about by helminth parasites Wuchereria bancrofti and Brugia malayi. Treatment of patients suffering from TPE involves the administration of diethyl carbamazine and Ivermectin. Although the drugs are able to block acute inflammation, they are not able to alleviate chronic basal inflammation. We have attempted to examine the disease by targeting two important components; namely filarial parasitic sheath proteins (FPP) induced apoptosis and pro-inflammatory cytokine response in human laryngeal carcinoma cells of epithelial origin (HEp-2) cells an epithelial cell line. Earlier studies by us have shown that FPP exposure induced apoptosis in these cells. In this study with hydrocortisone, calpain inhibitor (ALLN) and phorbol myristate acetate (PMA) treatments we demonstrate that apoptosis is inhibited as shown by [3H] thymidine incorporation studies, propidium iodide staining and Annexin V staining. Hydrocortisone at a dose, which inhibits cell death also down regulated, the expression of pro-inflammatory cytokines IL-6 and IL-8. These findings give us insights into the multifaceted approach one may adopt to target critical signalling molecules using appropriate inhibitors, which could eventually be used to reduce lung damage in TPE.
Narayanan
Kishore
K
Centre for Biotechnology, Anna University, Chennai 600025, India.
Krishnamoorthy
Bhavani
B
Ezhilarasan
Ravesanker
R
Miyamoto
Shigeki
S
Balakrishnan
Arun
A
D002460:Cell Line; D016207:Cytokines / Q000037:antagonists & inhibitors / Q000096:biosynthesis* / Q000235:genetics; D004305:Dose-Response Relationship, Drug; D016503:Drug Delivery Systems / Q000379:methods*; D005786:Gene Expression Regulation / Q000187:drug effects / Q000502:physiology; D006023:Glycoproteins / Q000008:administration & dosage; D006801:Humans; D006854:Hydrocortisone / Q000008:administration & dosage; D007249:Inflammation / Q000188:drug therapy* / Q000378:metabolism; D008168:Lung / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D011657:Pulmonary Eosinophilia / Q000188:drug therapy* / Q000378:metabolism; D015398:Signal Transduction / Q000187:drug effects* / Q000502:physiology; D013755:Tetradecanoylphorbol Acetate / Q000008:administration & dosage
D016207:Cytokines; D006023:Glycoproteins; C039304:calpain inhibitors; D013755:Tetradecanoylphorbol Acetate; D006854:Hydrocortisone