| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH |
|
|
|
|||||||
|
|||||||||
Published online before print October 4, 2006
| ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Article |
,
,
Departments of *Biomolecular Chemistry and Pediatrics, University Wisconsin-Madison, Wisconsin, USA; and Department of Chemistry, Lawrence University, Appleton, Wisconsin, USA
@ To whom correspondence should be addressed. E-mail: pbertics{at}wisc.edu.
 |
Abstract |
|---|
Human rhinovirus (HRV)-induced respiratory infections are associated with elevated levels of IFN-
-inducible protein 10 (IP-10), which is an enhancer of T lymphocyte chemotaxis and correlates with symptom severity and T lymphocyte number. Increased IP-10 expression is exhibited by airway epithelial cells following ex vivo HRV challenge and requires intracellular viral replication; however, there are conflicting reports regarding the necessity of type I IFN receptor ligation for IP-10 expression. Furthermore, the involvement of resident airway immune cells, predominantly bronchoalveolar macrophages, in contributing to HRV-stimulated IP-10 elaboration remains unclear. In this regard, our findings demonstrate that ex vivo exposure of human peripheral blood monocytes and bronchoalveolar macrophages (monocytic cells) to native or replication-defective HRV serotype 16 (HRV16) resulted in similarly robust levels of IP-10 release, which occurred in a time- and dose-dependent manner. Furthermore, HRV16 induced a significant increase in type I IFN (IFN-
) release and STAT1 phosphorylation in monocytes. Neutralization of the type I IFN receptor and inhibition of JAK or p38 kinase activity strongly attenuated HRV16-stimulated STAT1 phosphorylation and IP-10 release. Thus, this work supports a model, wherein HRV16-induced IP-10 release by monocytic cells is modulated via autocrine/paracrine action of type I IFNs and subsequent JAK/STAT pathway activity. Our findings demonstrating robust activation of monocytic cells in response to native and/or replication-defective HRV16 challenge represent the first evidence indicating a mechanistic disparity in the activation of macrophages when compared with epithelial cells and suggest that macrophages likely contribute to cytokine elaboration following HRV challenge in vivo.
Key Words: monocyte/macrophage • signal transduction • inflammation
This article has been cited by other articles:
|
|
 |
|
  M. Ruhwald, T. Bodmer, C. Maier, M. Jepsen, M. B. Haaland, J. Eugen-Olsen, P. Ravn, and on behalf of TBNET Evaluating the potential of IP-10 and MCP-2 as biomarkers for the diagnosis of tuberculosis Eur. Respir. J., December 1, 2008; 32(6): 1607 - 1615. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 M. L. Gavala, Z. A. Pfeiffer, and P. J. Bertics The nucleotide receptor P2RX7 mediates ATP-induced CREB activation in human and murine monocytic cells J. Leukoc. Biol., October 1, 2008; 84(4): 1159 - 1171. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 B G G Oliver, S Lim, P Wark, V Laza-Stanca, N King, J L Black, J K Burgess, M Roth, and S L Johnston Rhinovirus exposure impairs immune responses to bacterial products in human alveolar macrophages Thorax, June 1, 2008; 63(6): 519 - 525. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 K. Liu, R. C. Gualano, M. L. Hibbs, G. P. Anderson, and S. Bozinovski Epidermal Growth Factor Receptor Signaling to Erk1/2 and STATs Control the Intensity of the Epithelial Inflammatory Responses to Rhinovirus Infection J. Biol. Chem., April 11, 2008; 283(15): 9977 - 9985. [Abstract] [Full Text] [PDF]
|
|
| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH |
