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Molecular mechanisms of Th2 inflammation in the lung
Pulmonary inflammation, particularly Th2 inflammation, is an important immune response that underlies many diseases, including asthma and COPD. Cytokines, chemokines, and other factors play important roles in initiation, regulation, and resolution of inflammation in the lung. Our laboratory is interested in understanding the molecular mechanisms and specific pathways that regulate inflammation. Many of our studies utilize animal models of allergen induced, cytokine induced, and spontaneous inflammatory responses in the lung. These include allergen sensitization and challenge models, transgenic models in which specific cytokines or factors are targeted to the lung, and natural mutant models. Using these models and techniques we will be able to identify novel molecules and pathways that mediate or regulate pulmonary inflammation. These studies will help us in testing new therapeutic strategies for the treatment of inflammatory pulmonary disease such as asthma and COPD.
Zhou Zhu, MD, PhD
Associate Professor of Medicine
Sun-Young Oh, PhD
Instructor of Medicine
Fan Wu, BS
Baojun Yuan, MD
Li Zhou, BS
Research Publications (last 6 years)
1. Ma, B., Zhu, Z., Homer, R.J., Gerard, C., Strieter, R., and Elias, J.A. 2004. The C10/CCL6 Chemokine and CCR1 Play Critical Roles in the Pathogenesis of IL-13-Induced Inflammation and Remodeling. J Immunol 172:1872-1881.
2. Zhu Z., T. Zheng, R. J. Homer, Y-K Kim, N. Y. Chen, L. Cohn, Q. Hamid, and J. A. Elias. 2004. Acidic Mammalian Chitinase in Asthma Th2 Inflammation and IL-13 Pathway Activation. Science 304:1678-82.
3. Jiang, DH, Liang, J., Hodge, J., Lu, B., Zhu, Z., Yu, S., Fan, J., Gao, Y.F., Yin, Z., Homer, R.J., Gerard, C., and Noble, P. 2004. Regulation of Pulmonary Fibrosis by Chemokine Receptor CXCR3. J Clin Invest 114:291-299.
4. He CH, Waxman AB, Lee CG, Link H, Rabach ME, Ma B, Chen Q, Zhu Z, Zhong M, Nakayama K, Nakayama KI, Homer R, Elias JA. 2005. Bcl-2-related protein A1 is an endogenous and cytokine-stimulated mediator of cytoprotection in hyperoxic acute lung injury. J Clin Invest. 115(4):1039-48.
5. Zheng T, Kang MJ, Crothers K, Zhu Z, Liu W, Lee CG, Rabach LA, Chapman HA, Homer RJ, Aldous D, De Sanctis GT, Underwood S, Graupe M, Flavell RA, Schmidt JA, Elias JA. 2005. Cathepsin S-dependent epithelial cell apoptosis is a critical event in pulmonary apoptosis. J. Immunol 174(12):8106-15.
6. Zheng T, Rabach M, Chen NY, Rabach L, Hu X, Elias JA, Zhu Z. 2005. Molecular cloning and functional characterization of mouse chitotriosidase. Gene. 357(1):37-46.
7. Park, H., Li, Z., Yang, X.O., Chang, S.H., Nurieva, R., Wang, Y.H., Wang, Y., Hood, L., Zhu, Z., Tian, Q., Dong, C. 2005. A distinct lineage of CD4 T cells regulates tissue inflammation by producing interleukin 17. Nat Immunol 6:1133-1141.
8. Mizue, Y., Ghani, S., Leng, L., McDonald, C., Kong, P., Baugh, J., Lane, S.J., Craft, J., Nishihira, J., Donnelly, S.C., Zhu, Z. Bucala, R. 2005. Role for macrophage migration inhibitory factor in asthma. Proc Natl Acad Sci U S A 102:14410-14415.
9. Bhandari, V., R. Choo-Wing, C.G. Lee, Z. Zhu, J.H. Nedrelow, G.L. Chupp, X. Zhang, M.A. Matthay, L.B. Ware, R.J. Homer, P.J. Lee, A. Geick, A.R. de Fougerolles, and J.A. Elias. 2006. Hyperoxia causes angiopoietin 2-mediated acute lung injury and necrotic cell death. Nat Med 12:1286-1293.
10. Shim, Y.M., Z. Zhu, T. Zheng, C.G. Lee, R.J. Homer, B. Ma, and J.A. Elias. 2006. Role of 5-lipoxygenase in IL-13-induced pulmonary inflammation and remodeling. J Immunol 177:1918-1924.
11. Homer, R.J., Z. Zhu, L. Cohn, C.G. Lee, W.I. White, S. Chen, and J.A. Elias. 2006. Differential expression of chitinases identify subsets of murine airway epithelial cells in allergic inflammation. Am J Physiol Lung Cell Mol Physiol 291:L502-511.
12. Lee, P.J., X. Zhang, P. Shan, B. Ma, C.G. Lee, R.J. Homer, Z. Zhu, M. Rincon, B.T. Mossman, and J.A. Elias. 2006. ERK1/2 mitogen-activated protein kinase selectively mediates IL-13-induced lung inflammation and remodeling in vivo. J Clin Invest 116:163-173.
13. Zhou, W., K. Hashimoto, M.L. Moore, J.A. Elias, Z. Zhu, J. Durbin, G. Colasurdo, J.A. Rutigliano, C.L. Chiappetta, K. Goleniewska, J.F. O'Neal, B.S. Graham, and R.S. Peebles, Jr. 2006. IL-13 is associated with reduced illness and replication in primary respiratory syncytial virus infection in the mouse. Microbes Infect 8:2880-2889.
14. Oh, S.Y., T. Zheng, M.L. Bailey, D.L. Barber, J.T. Schroeder, Y.K. Kim, and Z. Zhu. 2007. Src homology 2 domain-containing inositol 5-phosphatase 1 deficiency leads to a spontaneous allergic inflammation in the murine lung. J Allergy Clin Immunol 119:123-131.
15. Kim, Y.K., S.Y. Oh, S.G. Jeon, H.W. Park, S.Y. Lee, E.Y. Chun, B. Bang, H.S. Lee, M.H. Oh, Y.S. Kim, J.H. Kim, Y.S. Gho, S.H. Cho, K.U. Min, Y.Y. Kim, and Z. Zhu. 2007. Airway Exposure Levels of Lipopolysaccharide Determine Type 1 versus Type 2 Experimental Asthma. J Immunol 178:5375-5382.
16. Angkasekwinai, P., H. Park, Y.H. Wang, Y.H. Wang, S.H. Chang, D.B. Corry, Y.J. Liu, Z. Zhu, and C. Dong. 2007. Interleukin 25 promotes the initiation of proallergic type 2 responses. J Exp Med 204:1509-1517.
17. Jeon SG, Oh SY, Park HK, Kim YS, Shim EJ, Lee HS, Oh MH, Bang B, Chun EY, Kim SH, Gho YS, Zhu Z, Kim YY, Kim YK. 2007. TH2 and TH1 lung inflammation induced by airway allergen sensitization with low and high doses of double-stranded RNA. J Allergy Clin Immunol 120:803-812.
18. Zheng, T., W. Liu, S.Y. Oh, Z. Zhu, B. Hu, R.J. Homer, L. Cohn, M.J. Grusby, and J.A. Elias. 2008. IL-13 Receptor a2 Selectively Inhibits IL-13-Induced Responses in the Murine Lung. J Immunol 180:522-529.
19. Yang X.O., S.H. Chang, H. Park, R. Nurieva, B. Shah, L. Acero, Y.H. Wang, K.S. Schluns, R.R. Broaddus, Z. Zhu, C. Dong. 2008. Regulation of inflammatory responses by IL-17F. J Exp Med 205:1063-1075.
20. Cho, Y. S., S. Y. Oh, and Z. Zhu. 2008. Tyrosine Phosphatase SHP-1 in Oxidative Stress and Development of Allergic Airway Inflammation. Am J Respir Cell Mol Biol 39(4):412-9.
21. Jeon, S. G., H. G. Moon, Y. S. Kim, J. P. Choi, T. S. Shin, S. W. Hong, Y. M. Tae, S. H. Kim, Z. Zhu, Y. S. Gho, and Y. K. Kim. 2009. 15-lipoxygenase metabolites play an important role in the development of a T-helper type 1 allergic inflammation induced by double-stranded RNA. Clin Exp Allergy 39:908-917.
22. Oh S.Y., T. Zheng, Y.K. Kim, L. Cohn, R.J. Homer, A.N. McKenzie, Z. Zhu. 2009. A Critical Role of SHP-1 in Regulation of Type 2 Inflammation in the Lung. Am J Respir Cell Mol Biol. 40(5):568-74.
23. Zheng T, Oh MH, Oh SY, Schroeder JT, Glick AB, Zhu Z. 2009. Transgenic expression of interleukin-13 in the skin induces a pruritic dermatitis and skin remodeling. J Invest Dermatol. 129(3):742-51.
24. Yu, Q., A. Sharma, S. Y. Oh, H. G. Moon, M. Z. Hossain, T. M. Salay, K. E. Leeds, H. Du, B. Wu, M. L. Waterman, Z. Zhu, and J. M. Sen. 2009. T cell factor 1 initiates the T helper type 2 fate by inducing the transcription factor GATA-3 and repressing interferon-gamma. Nat Immunol 10:992-999.
25. Kim, Y. S., S. W. Hong, J. P. Choi, T. S. Shin, H. G. Moon, E. J. Choi, S. G. Jeon, S. Y. Oh, Y. S. Gho, Z. Zhu, and Y. K. Kim. 2009. Vascular Endothelial Growth Factor Is a Key Mediator in the Development of T Cell Priming and Its Polarization to Type 1 and Type 17 T Helper Cells in the Airways. J Immunol. 183:5113-5120.
26. Guo, J. P., M. E. Brummet, A. C. Myers, H. J. Na, E. Rowland, R. L. Schnaar, T. Zheng, Z. Zhu and B. S. Bochner. 2010. Characterization of expression of glycan ligands for Siglec-F in normal mouse lungs. Am J Respir Cell Mol Biol Accepted.
27. Jang, M. K., S. H. Kim, K. Y. Lee, T. B. Kim, K. A. Moon, C. S. Park, Y. J. Bae, Z. Zhu, H. B. Moon, and Y. S. Cho. 2010. The tyrosine phosphatase, SHP-1, is involved in bronchial mucin production during oxidative stress. Biochem Biophys Res Commun 393:137-143.
28. Yeh, Y. C., L. Xie, J. M. Langdon, A. C. Myers, S. Y. Oh, Z. Zhu, and S. M. Macdonald. 2010. The effects of overexpression of histamine releasing factor (HRF) in a transgenic mouse model. PLoS One 5:e11077.
29. Zhang, L., S. Y. Oh, X. Wu, M. H. Oh, F. Wu, J. T. Schroeder, C. M. Takemoto, T. Zheng, and Z. Zhu. 2010. SHP-1 deficient mast cells are hyperresponsive to stimulation and critical in initiating allergic inflammation in the lung. J Immunol 184:1180-1190.
30. Choi, J. P., Y. S. Kim, Y. M. Tae, E. J. Choi, B. S. Hong, S. G. Jeon, Y. S. Gho, Z. Zhu, and Y. K. Kim. 2010. A viral PAMP double-stranded RNA induces allergen-specific Th17 cell response in the airways which is dependent on VEGF and IL-6. Allergy (Published online April 2010).
31. Moon, H. G., Y. M. Tae, Y. S. Kim, S. Gyu Jeon, S. Y. Oh, Y. Song Gho, Z. Zhu, and Y. K. Kim. 2010. Conversion of Th17-type into Th2-type inflammation by acetyl salicylic acid via the adenosine and uric acid pathway in the lung. Allergy (Published online March 2010).
32. Shin, T. S., J. H. Kim, Y. S. Kim, S. G. Jeon, Z. Zhu, Y. S. Gho, and Y. K. Kim. 2010. Extracellular vesicles are key intercellular mediators in the development of immune dysfunction to allergens in the airways. Allergy (Published online 10 March 2010).
33. Oh, S. Y., J. U. Park, T. Zheng, Y. K. Kim, F. Wu, S. H. Cho, D. Barber, J. Penninger, and Z. Zhu. 2010. Cbl-b Regulates Airway Mucosal Tolerance to Aeroallergen. Clin. Exp. Allergy (Accepted).
Updated July 2010