This Article Full Text Full Text (PDF) Alert me when this article is cited Alert me if a correction is posted Services Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Roy, B. Articles by Cathcart, M. K. Search for Related Content PubMed PubMed Citation Articles by Roy, B. Articles by Cathcart, M. K.

(Journal of Leukocyte Biology. 2002;72:580-589.)
© 2002 by Society for Leukocyte Biology

IL-13 signal transduction in human monocytes: phosphorylation of receptor components, association with Jaks, and phosphorylation/activation of Stats

Biswajit Roy^*, Ashish Bhattacharjee^*, Bo Xu^*, Dwayne Ford, Abby L. Maizel and Martha K. Cathcart^*

^* Department of Cell Biology, Lerner Research Institute, Cleveland Clinic Foundation, Ohio; and
Roger Williams Medical Center, Boston University, School of Medicine, Massachusetts

Correspondence: Dr. Martha K. Cathcart, Department of Cell Biology/NC10, Lerner Research Institute, Cleveland Clinic Foundation, 9500 Euclid Avenue, Cleveland, OH 44195. E-mail: cathcam{at}ccf.org

Interleukin (IL)-13 regulates monocyte function and is a potent stimulator of 15-lipoxygenase expression. In different cell types, the functional IL-13 receptor complex can be comprised of variable protein components and has not been thoroughly examined in human monocytes. Here, we identify the receptor components and upstream signaling events initiated by IL-13 in primary human blood monocytes. The expression, phosphorylation and associated Jak kinases of the known, variable receptor components, IL-4R, IL-2Rc, IL-13R1 and IL-13R2, were examined. We determined that IL-4R and IL13R1 are phosphorylated upon exposure to IL-13. Although IL-2Rc is also expressed, it is not phosphorylated upon exposure to IL-13. Evaluation of the presence of IL-13R2 failed to reveal significant mRNA or protein expression. Earlier, our laboratory showed that IL-13 induced the phosphorylation of Jak2 and Tyk2 in monocytes and that expression of both Jaks was essential for downstream signaling by IL-13. Here, we report that Jak2 is associated with IL-4R, and Tyk2 is associated with the IL-13R1 component of the IL-13 receptor complex. Additionally, Stat proteins 1, 3, 5A, 5B, and 6 are phosphorylated in response to IL-13. Further, the nuclear translocation and DNA binding of each of these Stats were induced by IL-13. These data represent the first complete report of the functional IL-13 receptor complex and early signaling events in human monocytes. This information is critical for understanding the IL-13 response of monocytes in inflammation.

Key Words: human macrophages • cytokine receptors • cytokines • inflammation • monocytes

This article has been cited by other articles:

				S. R. White, L. D. Martin, M. K. Abe, B. A. Marroquin, R. Stern, and X. Fu Insulin receptor substrate-1/2 mediates IL-4-induced migration of human airway epithelial cells Am J Physiol Lung Cell Mol Physiol, July 1, 2009; 297(1): L164 - L173. [Abstract] [Full Text] [PDF]

				H. K. Jessup, A. W. Brewer, M. Omori, E. A. Rickel, A. L. Budelsky, B.-R. P. Yoon, S. F. Ziegler, and M. R. Comeau Intradermal Administration of Thymic Stromal Lymphopoietin Induces a T Cell- and Eosinophil-Dependent Systemic Th2 Inflammatory Response J. Immunol., September 15, 2008; 181(6): 4311 - 4319. [Abstract] [Full Text] [PDF]

				A. Bhattacharjee, B. Xu, D. A. Frank, G. M. Feldman, and M. K. Cathcart Monocyte 15-Lipoxygenase Expression Is Regulated by a Novel Cytosolic Signaling Complex with Protein Kinase C {delta} and Tyrosine-Phosphorylated Stat3 J. Immunol., September 15, 2006; 177(6): 3771 - 3781. [Abstract] [Full Text] [PDF]

				K. J. Savage Primary mediastinal large B-cell lymphoma. Oncologist, May 1, 2006; 11(5): 488 - 495. [Abstract] [Full Text] [PDF]

				A. Lorentz, M. Wilke, G. Sellge, H. Worthmann, J. Klempnauer, M. P. Manns, and S. C. Bischoff IL-4-Induced Priming of Human Intestinal Mast Cells for Enhanced Survival and Th2 Cytokine Generation Is Reversible and Associated with Increased Activity of ERK1/2 and c-Fos J. Immunol., June 1, 2005; 174(11): 6751 - 6756. [Abstract] [Full Text] [PDF]

				M. A. Shipp, S. L. Aquino, and N. L. Harris Case 12-2005 - A 30-Year-Old Woman with a Mediastinal Mass N. Engl. J. Med., April 21, 2005; 352(16): 1697 - 1704. [Full Text] [PDF]

				P. Chaitidis, E. E. Billett, V. B. O'Donnell, A. B. Fajardo, J. Fitzgerald, R. J. Kuban, U. Ungethuem, and H. Kuhn Th2 Response of Human Peripheral Monocytes Involves Isoform-Specific Induction of Monoamine Oxidase-A J. Immunol., October 15, 2004; 173(8): 4821 - 4827. [Abstract] [Full Text] [PDF]

				B. Xu, A. Bhattacharjee, B. Roy, G. M. Feldman, and M. K. Cathcart Role of Protein Kinase C Isoforms in the Regulation of Interleukin-13-induced 15-Lipoxygenase Gene Expression in Human Monocytes J. Biol. Chem., April 16, 2004; 279(16): 15954 - 15960. [Abstract] [Full Text] [PDF]

				K. J. Savage, S. Monti, J. L. Kutok, G. Cattoretti, D. Neuberg, L. de Leval, P. Kurtin, P. D. Cin, C. Ladd, F. Feuerhake, et al. The molecular signature of mediastinal large B-cell lymphoma differs from that of other diffuse large B-cell lymphomas and shares features with classical Hodgkin lymphoma Blood, December 1, 2003; 102(12): 3871 - 3879. [Abstract] [Full Text] [PDF]

				B. Xu, A. Bhattacharjee, B. Roy, H.-M. Xu, D. Anthony, D. A. Frank, G. M. Feldman, and M. K. Cathcart Interleukin-13 Induction of 15-Lipoxygenase Gene Expression Requires p38 Mitogen-Activated Protein Kinase-Mediated Serine 727 Phosphorylation of Stat1 and Stat3 Mol. Cell. Biol., June 1, 2003; 23(11): 3918 - 3928. [Abstract] [Full Text] [PDF]

				Y. Seto, H. Nakajima, A. Suto, K. Shimoda, Y. Saito, K. I. Nakayama, and I. Iwamoto Enhanced Th2 Cell-Mediated Allergic Inflammation in Tyk2-Deficient Mice J. Immunol., January 15, 2003; 170(2): 1077 - 1083. [Abstract] [Full Text] [PDF]