Department of Pediatrics
The Ellrodt-Schweighauser Family Chair of Perinatal Research
Contact Information:
Email: tjilling@northshore.org
Medical School: MD, University Medical School Pécs, Hungary. Current name of school: University of Pécs, Faculty of Medicine
Fellowship: Postdoctoral Fellow, Department of Physiology and Biophysics, University of Alabama at Birmingham
Research Fellow: Cystic Fibrosis Foundation (USA), Department of Physiology and Biophysics, University of Alabama at Birmingham
Honors and Awards:
- Scholarship of the University Medical School Pécs for student researchers, 1985-1987.
- Scholarship of the Hungarian Academy of Sciences, 1987-1989.
- Research Fellowship of the Cystic Fibrosis Foundation (USA), 1990-1993.
- The Jessica Jacobi Golder Endowment, 1997–2006.
- Ellrodt-Schweighauser Family Chair of Perinatal Research, 2006–present.
Professional Affiliations/Activities:
- American Society for Cell Biology, 1993-present.
- International Society for Research on Human Milk and Lactation, 1999-present.
- Society for Pediatric Research, 2002-present.
- American Physiological Society, 2003-present.
Research Interests:
Modulation of mucosal inflammation by epithelial cells: Inflammation on mucosal surfaces underlies many disease states, such as inflammatory bowel disease, necrotizing enterocolitis, asthma, cystic fibrosis, and emphysema. Our lab’s interests focus on the role of epithelial cells in mucosal inflammatory homeostasis. We use techniques of cell biology, biochemistry, electrophysiology and molecular biology to investigate mechanisms of epithelial cell contribution to mucosal inflammation, and to study inflammatory regulation of epithelial functions.
Necrotizing enterocolitis (NEC): NEC is a sudden, inflammatory necrosis of the intestinal wall, occurring during the first few weeks of life, and almost exclusively in prematurely born babies. It is one of the most prevalent, often lethal complications of premature birth and, due to lengthy and costly acute treatment as well as consequent lifelong complications in survivors, NEC poses severe burden on both individual and society. The etiology of this disease is poorly understood, thus, preventive, diagnostic, and treatment strategies are also in their infancy. Our laboratory has made important contributions to the identification of several key mechanisms and mediators that underlie NEC pathogenesis, including the role of accelerated enterocyte apoptosis, a central role for the small, phospholipid inflammatory mediator platelet-activating factor (PAF), and the role of erroneous host-pathogen interactions via toll-like receptors.
The PAF receptor (PAFR) is a member of the large receptor superfamily of seven transmembrane domain, G protein-coupled receptors (GPCR). Similar to many other members of this family, the PAF receptor is covalently modified by acylation (i.e., palmitoylated) on its C terminus cytoplasmic tail. Current efforts in our lab focus on the characterization of the role of palmitoylation in the polarized targeting, endocytic trafficking and signaling of the PAF receptor. We have shown that polyunsaturated fatty acids (PUFA) can dampen deleterious consequences of PAFR activation in cellular and animal models of NEC. Our results indicate that these effects are due to a novel mechanism, involving the modification of PAFR palmitoylation by PUFA. These studies may lead to identification of novel preventive strategies for NEC by aiding the design of improved formulations for premature infant formula.
One of the key components in host-pathogen interactions are toll-like receptors (TLR), which are part of the innate immune system (i.e., part of our immune system which functions to recognize pathogens without “immunological learning”). Signaling via two of these receptors, TLR4 and TLR2, is subdued or muted in mature or normally developing intestinal epithelium, while it is increased in experimental NEC. Our recent studies identified an important crosstalk between signaling via TLR-s and the PAFR, which may underlie the aberrantly increased TLR signaling in experimental NEC. A better understanding of dysregulated TLR signaling and its relationship to PAFR signaling may lead to new preventive or therapeutic strategies for NEC.
Selected References:
Jilling T, Cunningham S, Barker PE, Green MW, Frizzell RA, and Kirk KL. Genetic complementation in cystic fibrosis pancreatic cells by somatic cell fusion. Am J Physiol 259:C1010-1015, 1990.
Jilling T and Kirk KL. Cyclic AMP and chloride-dependent regulation of the apical constitutive secretory pathway in colonic epithelial cells. J Biol Chem 271:4381-4387, 1996.
Jilling T, Lu J, Jackson M, and Caplan MS. Intestinal epithelial apoptosis initiates gross bowel necrosis in an experimental rat model of neonatal necrotizing enterocolitis. Pediatr Res 55:622-629, 2004.
Lu J, Caplan MS, Saraf AP, Li D, Adler L, Liu X, and Jilling T. Platelet-activating factor-induced apoptosis is blocked by Bcl-2 in rat intestinal epithelial cells. Am J Physiol Gastrointest Liver Physiol 286:G340-350, 2004.
Jilling T, Simon D, Lu J, Meng FJ, Li D, Schy R, Thomson RB, Soliman A, Arditi M, Caplan MS. The roles of bacteria and TLR4 in rat and murine models of necrotizing enterocolitis. J Immunol 177:3273-3282. 2006
Claud EC, Lu J, Wang XQ, Abe M, Petrof EO, Sun J, Nelson DJ, Marks J, and Jilling T. Platelet-activating factor-induced chloride channel activation is associated with intracellular acidosis and apoptosis of intestinal epithelial cells. Am J Physiol Gastrointest Liver Physiol 294:G1191-1200, 2008.
Lu J, Caplan MS, Li D, and Jilling T. Polyunsaturated fatty acids block platelet-activating factor-induced phosphatidylinositol 3 kinase/Akt-mediated apoptosis in intestinal epithelial cells. Am J Physiol Gastrointest Liver Physiol 294:G1181-1190, 2008.
Editorial Board Memberships:
Clinical Medicine Insights: Gastroenterology, 2008–present.
International Journal of Physiology, Pathophysiology and Pharmacology, 2010-present.
Manuscript Reviewer for:
American Journal of Gastroenterology
AJP Cell Physiology
AJP Gastrointestinal and Liver Physiology
Cell Motility and the Cytoskeleton
Journal of General Physiology
Journal of Clinical Investigation
Pediatric Research
Physiological Chemistry and Physics and Medical NMR
BBA
PlosOne
Developmental Neuroscience
Clinical Science
Gastroenterology
J. Immunology
Neonatology
Grant review activity:
Pilot Project Review Committee, NorthShore University HealthSystem Research Institute, 2003–present.
Mail in Reviewer, MABS/NIH CSR, 2006.
Mail in Reviewer, NIH/CSR, 2009.
The Wellcome Trust (UK), 2009.
Reviews and chapters:
Jilling T. and Kirk K.L. Fluorescence digital imaging microscopy in epithelial biology. IN: Methods in Membrane and Transporter Research, Molecular Biology Intelligence Unit, R.G. Landes Co., pp. 177-214, 1994. (book chapter)
Jilling T. and Kirk K.L. The biogenesis, traffic and function of the Cystic Fibrosis Transmembrane Conductance Regulator. International Review of Cytology, 172:193 - 241, 1997. (invited review)
Caplan, M.S. and Jilling T. 2001. Neonatal necrotizing enterocolitis: Possible role of probiotic supplementation. J Pediatr Gastroenterol Nutr, 30(Suppl 2):S18-22. (invited review)
Caplan MS, Jilling T. New concepts in necrotizing enterocolitis. Curr Opin Pediatr, 13:111+.
Caplan MS, Amer M, and Jilling T. The role of human milk in necrotizing enterocolitis. Adv Exp Med Biol 503:83-90, 2002. (invited review)
Jilling T. The Biology of Cystic Fibrosis. In: Disease Markers in Exhaled Breath: Basic Mechanisms and Clinical Applications, edited by Marczin N and Yacoub MH. Amsterdam: IOS Press, 2002. (book chapter)
Caplan MS, Amer M, Jilling T. 2002. The role of human milk in necrotizing enterocolitis. Adv Exp Med Biol 503:83-90. (invited review)
Caplan MS, Simon D, Jilling T. The role of PAF, TLR, and the inflammatory response in neonatal necrotizing enterocolitis. Semin Pediatr Surg 2005; 14:145-51. (invited review)
Caplan MS, Jilling T. Neonatal necrotizing enterocolitis: clinical observations and pathophysiology. In: Thureen PJ, Hay WW, eds. Neonatal nutrition and metabolism. 2nd ed. Cambridge, UK: New York : Cambridge University Press, 2006:482-491. (book chapter)