Alveolar epithelial and macrophage interactions in modulating the pulmonary injury response during post-natal development.

Among the environmental factors relevant to developmental lung disease are the recent increase in complexity and distribution, if not the levels, of airborne pollutants, including allergens and endotoxins, respirable particulate matter and irritant gases, To date, very little work has focused on complex mixtures, especially as they affect postnatal lung development. Exposure to complex and possibly even more toxic pollutant mixtures damages various cell types and activates multiple transcription factors. Multiple toxicants may result in responses not predicted by evaluating exposures to an individual toxicant. Similarly, recent studies suggest individuals with preexisting lung disease may be at increased risk for injury.

Our current working hypothesis is that many of these processes are regulated through intercellular communication by the production of and response to specific mediators that modulate and program cellular functions. We have identified a number of key cytokines, chemokines and growth factors, which induce epithelial proliferation and differentiation and are actively synthesized and secreted by epithelial cells. We are currently examining transcriptional and post–transcriptional regulation of these genes in pulmonary epithelial cells and resident inflammatory cells.

Johnston CJ, Holm BA, Finkelstein JN. 2006. Postnatal lung development: immediate-early gene responses post ozone and LPS exposure.. Inh Tox. 19:875-883.

Vitiello PF, Staversky RJ, Gehen SC, Johnston CJ, Finkelstein JN, Wright TW, O’Reilly MA. 2006. p21Cip1 protection against hyperoxia requires Bcl-XL and is uncoupled from its ability to suppress growth. Am J Pathol. Jun;168(6):1838-1847.

Elder A, Johnston C, Gelein R, Finkelstein J, Wang Z, Notter R, Oberdorster G. 2005. Lung inflammation induced by endotoxin is enhanced in rats depleted of alveolar macrophages with aerosolized clodronate. Exp Lung Res. Jul-Aug;31(6):527-546.

Wang J, Gigliotti F, Maggirwar S, Johnston C, Finkelstein JN, Wright TW. 2005. Pneumocystis carinii activates the NF-kappaB signaling pathway in alveolar epithelial cells. Infect Immun. May;73(5):2766-2777.

Johnston CJ, Holm BA, Finkelstein JN. 2005. Sequential exposures to ozone and lipopolysaccharide in postnatal lung enhance or inhibit cytokine responses. Exp Lung Res. May;31(4):431-447.

Johnston CJ, Holm BA, Finkelstein JN. 2004. Differential proinflammatory cytokine responses of the lung to ozone and lipopolysaccharide exposure during postnatal development. Exp Lung Res. Oct-Nov;30(7):599-614.

Johnston CJ, Williams JP, Elder A, Hernady E, and Finkelstein JN. 2004. Inflammatory cell recruitment following thoracic irradiation. Exp Lung Res. Jul-Aug;30(5):369-382.

Williams JP, Hernady E, Johnston CJ, Reed CM, Fenton B, Okunieff P, and Finkelstein JN. 2004. Effect of administration of lovastatin on the development of late pulmonary effects after whole-lung irradiation in a murine model. Radiat Res. 2004 May;161(5):560-567.

Finkelstein JN, and Johnston CJ. 2004. Enhanced sensitivity of the postnatal lung to environmental insults and oxidant stress. Pediatrics. Apr;113(4 Suppl):1092-1096. Review.

D’Angio CT, LoMonaco MB, Johnston CJ, Reed CK, and Finkelstein JN. 2004. Differential roles for NF-kappa B in endotoxin and oxygen induction of interleukin-8 in the macrophage. Am J Physiol Lung Cell Mol Physiol. Jan;286(1):L30-36.

Johnston CJ, Oberdörster G, Gelein R Finkelstein JN. 2002. Endotoxin potentiates ozone-induced pulmonary chemokine and inflammatory responses. Exp Lung Res 28(6): 419-433.

Johnston CJ, Williams JP, Okunieff, P, Finkelstein JN. 2002. Radiation–induced pulmonary fibrosis: Examination of chemokine and chemokine receptor families. Radiat Res 157(3): 256-265.