The major focus of our research is to determine the role of mast cells in the regulation of innate immune mechanisms and inflammatory response and to elucidate their contribution in the progression of cardiovascular disease and autoimmune diseases. Within this framework, our research encompasses a variety of distinct but interrelated disciplines which will determine how mast cell tryptase and histamine acting independently and in concert with microbial agents regulate the expression and function of Toll-like receptors, protease-activated receptors and cyclooxygenases in the vascular endothelium and heart.
Christ College, University of Kerala, India
M.S. University of Baroda, India
University of Delhi,
Children's Hospital Research Institute of Northern
California, Oakland, CA
School of Medicine, Indianapolis, IN
Faculty Appointment Date
Jehle, A.B., Stechschulte, A.C., Li, Y., Stechschulte, D.J, and Dileepan, K.N.: Production of IL-6 and IL-8 by endotoxin-activated human coronary artery endothelial cells is amplified by mast cell granule proteases. J. Interferon and Cytokine Research 20:361-368, 2000.
Wood, G.W., Hausmann, E.H.S., Choudhuri, R., and Dileepan, K.N.: Expression and regulation of histidine decarboxylase mRNA in the uterus during pregnacy in the mouse. Cytokine. 12: 622-629, 2000.
Li, Y., Chi, L., Stechschulte, D.J, and Dileepan, K.N.: Histamine-induced endothelial cell production of IL-6 and IL-8 is amplified by endotoxin and tumor necrosis factor-a. Microvascular Research, 61: 253-262, 2001.
Chi, L., Li, Y., Stehno-Bittel, L., Gao, J., Morrison, D.C., Stechschulte, D.J., and Dileepan, K.N.: Interleukin-6 production by endothelial cells via protease activated receptor stimulation is synegized by endotoxin and tumor necrosis factor-. J. Interferon and Cytokine Research. 231-240, 2001.
Chi, L., Li, Y., Stehno-Bittel, L, Stechschulte, D.J., and Dileepan, K.N.: Signal transduction pathways in mast cell granule-mediated endothelial cell activation. Mediators of Inflammation, 12: 79-87, 2003.
Johnston, T.P., Li, Y., Jamal, A.S., Stechschulte, D.J. and Dileepan, K.N.: Poloxymer 407 induced atherosclerotic lesions in mice appears to be due to lipid derangements and not due to its direct effects on endothelial cells and macrophages. Mediators of Inflammation, 12: 147-155, 2003.
Kennedy, M.N., Mullen, G.E.D, Leifer, C.A., Lee, C.W, Mazzoni, A., Dileepan, K.N., and Segal, D.M.: A complex of soluble MD-2 and lipopolysaccharide serves as an activating ligand for Toll-like receptor 4. J. Biol. Chem. 279: 34698-34704, 2004.
Talreja, J., Kabir, M.H., Filla, M., Stechschulte, D.J., and Dileepan, K.N.: Histamine induces Toll-like receptors 2 and 4 expression in endothelial cells and enhances sensitivity to Gram-positive and Gram-negative bacterial cell wall components. Immunology. 113: 224-233, 2004.
Dileepan, K.N., Johnston, T.P., Li, Y., Tawfik, O. and Stechschulte, D.J.: Deranged aortic intima-media thickness, plasma triglycerides and granulopoiesis in Sl/Sld mice. Mediators of Inflammation 13: 1-7, 2004.
Dileepan, K.N. and Stechschulte, D.J.: Endothelial cell activation by mast cell mediators. In “Methods in Molecular Biology: Mast Cell Protocols”, Eds. G. Krishnaswamy and D.C. Chi. Series editor, J.M. Walker. Humana Press, USA. 2005.
Nickel, T.J., Kabir, M.H., Talreja, J., Stechschulte, D.J., Dileepan, K.N.: Expression of functional protease-activated receptor 1 and 2 in human conjunctival epithelial cells. Mediators of Inflammation 2006 (3):61359. PMID: 16951492.
Talreja, J., Dileepan, K., Puri, S., Kabir, M.H., Segal,D.M., Stechschulte, D.J., and Dileepan, K.N.: Human conjunctival epithelial cells lack lipopolysaccharide responsiveness due to deficient expression of MD2 but respond after interferon- priming or MD2 supplementation. Inflammation 21: 170-181, 2006.
Sharma, R., Prasad, V., McCarthy, E.T., Savin, V.J., Dileepan, K.N., Stechschulte, D.J., Lianos, E., Wiegmann T., and Sharma, M. Chymase increases glomerular albumin permeability via protease-activated receptor-2. Mol. Cell. Biochem. 297: 161-169, 2007.
Tan, X, Essengue, S., Talreja, J., Stechschulte, D.J., and Dileepan, K.N. Histamine directly and synergistically stimulates cyclooxygenase-2 expression and prostaglandin I2 and prostaglandin E2 production in human coronary artery endothelial cells. J. Immunology 179: 7899 -7906, 2007.
Smith, D.D., Tan, X., Tawfik, O., Milne, G., Stechschulte, D.J., and Dileepan, K.N. Increased aortic atherosclerotic plaque development in female ApoE-/- mice is due to elevated thromboxane A2 and decreased prostacyclin production. J. Physiol. Pharmacol. 61:309-316, 2010.
Tan X., Poulose, E.M., Stechschulte, D.J., and Dileepan KN. Regulation of the expression of cyclooxygenases and the production of prostaglandin I2 prostaglandin E2 in human coronary artery endothelial cells by curcumin. J. Physiol. Pharmacol. 62:21-28, 2011.
Raveendran, V., Tan, X., Sweeney, M.E., Levant, B., Slusser, J., Stechschulte, D.J., and Dileepan, K.N. Lipopolysaccharide induces H1 receptor expression and enhances histamine responsiveness in human coronary artery endothelial cells. Immunology 132:578-588, 2011.
Walia, D.S., Sharma, M., Raveendran, V.V., Zhou, J., Sharma, R., Stechschulte, D.J., Dileepan, K.N. Human mast Cells (HMC-1 C56) enhance interleukin-6 production by quiescent and lipopolysaccharide-stimulated human coronary artery endothelial cells. Mediators of Inflammation. 2012: Article ID 274347, PMC32728, 2012.
Smith, D.D., Tan, X., Raveendran, V.V., Tawfik, O., Stechschulte, D.J., and Dileepan, K.N. Mast cell deficiency attenuates progression of atherosclerosis and hepatic steotosis in apolipoprotein E-null mouse, Am. J. Physiol., Heart & Circulatory Physiol. 302:H2612-H2621, 2012