Carol M. Artlett

Carol Artlett
Associate Professor
Microbiology and Immunology

Ph.D., 1996, University of London, London, United Kingdom

2900 Queen Lane
Philadelphia, PA 19129
Tel: 215-991-8585
Fax: 215-848-2271
Email: carol.artlett@drexelmed.edu

Research Staff: Sihem Sassi-Gaha
Graduate Students: Danielle Loughlin, Alicia Holmgren, Judy Reiger

Keywords:

allograft inflammatory factor-1, systemic sclerosis, 3-deoxyglucosone, autoimmunity, macrophage activation, inflammation

Research Interests:

We are interested in what mediates the scleroderma (SSc) phenotype by understanding the fibrotic and immunological events in these patients. SSc is a fibrotic disease of unknown origin that is predominantly found in women. What is apparent is the uncontrolled fibrosis in the dermis and internal organs that affects morbidity and leads to mortality in these patients. Understanding the mechanisms whereby fibroblasts interact with the extracellular matrix (ECM), are central to the understanding of fibrosis in SSc. Fibroblasts are sensitive to signals from the ECM and interaction of fibroblasts with the ECM is essential in many physiological and pathological processes. Integrins are important for transferring signals from the ECM into the cell and play an important role in regulating the efficiency of the RTK/Ras/ERK pathway. 3-Deoxyglucosone (3DG) is a highly reactive α-dicarbonyl that increases with chronological age and directly cross-links long-lived proteins such as collagen. It is known that the elderly frequently have less collagen in their skin and some have wound healing problems due to this. We observed that collagen cross-linked with 3DG caused a decrease in the expression of ECM proteins from normal and SSc fibroblasts cultured in vitro. The goals of investigators working in the laboratory are to understand the cellular signaling mechanisms whereby the collagen expression is decreased in 3DG cross-linked matrices.

The second area of interest is investigating the role of allograft inflammatory factor-1 (AIF-1) in the vascular complications of SSc. AIF-1 is expressed in inflammatory cells and is also expressed in infiltrating cells in the vessel wall and appears to mediate increase cellular replication of vascular smooth muscle cells. This leads to a narrowing of the lumen of the vessel and pulmonary hypertension. Patients with SSc frequently die of complications due to pulmonary hypertension. The goal of this research is to understand what modulates the expression of AIF-1, and ultimately, how to turn off its expression.

Publications:

Sawaya HHB, Jimenez SA, Artlett CM. Quantification of fetal microchimeric cells in clinically affected and unaffected skin of patients with systemic sclerosis. Rheumatology 43:965-8, 2004.
Kowalzick L, Artlett CM, Thoss K, Baum H-P, Ziegler H, Mischke D, Blum R, Ponnighaus J-M, Quietzsch J. Chronic graft versus host like dermopathy in a child with CD4+ cell microchimerism and successful treatment with UVA1 phototherapy. Dermatology 210: 68-71, 2005.
Jimenez SA, Artlett CM. Microchimerism and systemic sclerosis. Curr Opinion Rheumatol. 17: 86-90, 2005.
Artlett CM. Immunology of systemic sclerosis. Frontiers in Bioscience 10:1707 – 1719, 2005.
Artlett CM. Pathophysiology of fetal microchimeric cells. Clinica Chimica Acta 360:1-8, 2005.
Gentiletti, J, McCloskey LJ, Artlett CM, Peters J, Jimenez SA, Christner PJ. Demonstration of autoimmunity in the tight skin-2 mouse: a model for scleroderma. J. Immunol. 175:2418-26, 2005.
Kowalzick L, Artlett CM, Thoss K, Baum H-P, Zieger H, Mischke D, Blum R, Ponnighaus J-M, Quietzsch J. (Letter). Dermatology 211: 389, 2005.
Derk C, Artlett CM, Jimenez SA. Morbidity and mortality of patients diagnosed with systemic sclerosis after the age of 75: a nested case-control study. Clin Rheumatol 25:1-4, 2006.
Mendoza FA, Artlett CM, Sandorfi N, Latinis K, Piera-Velazquez S, Jimenez SA. Description of 12 cases of nephrogenic fibrosing dermopathy and review of the literature. Semin Arthritis Rheum 35:238-249, 2006.
Del Galdo F, Artlett CM. T cells and B cells in the Pathogenesis of SSc: Recent Insights and Therapeutic Opportunities. Curr Rheumatol Rep 8:123-30, 2006.
Derk CT, Rasheed M, Artlett CM, Jimenez SA. A cohort study of cancer incidence in systemic sclerosis. J Rheumatol 33: 1113-6, 2006.
Del Galdo F, Jimenez SA, Artlett CM. Tissue expression of allograft inflammatory factor-1 in systemic sclerosis and in vitro differential expression of its isoforms in response to transforming growth factor-beta. Arthritis Rheum 54: 2616-25, 2006.
Del Galdo G, Artlett CM, Jimenez SA. The role of allograft inflammatory factor 1 in systemic sclerosis. Curr Opin Rheumatol., 18:588-93, 2006.

Otieno FG, Lopez AM, Jimenez SA, Gentiletti J, Artlett CM. Allograft inflammatory factor-1 and tumor necrosis factor single nucleotide polymorphism in systemic sclerosis. Tissue Antigens, 69: 583 – 91, 2007.
Mueller, Y. M., Duc, H. D., Altork, S. R., Artlett, C. M., Graceley, E. J., Katsetos, C. D., Legido, A., Villinger, F., Altman, J. D., Brown, C. R., Lewis, M. G., and P. D. Katsikis. IL-15 treatment during acute SIV infection increases viral set point and accelerates disease progression. J. Immunol., 180: 350-360, 2008.