J Virol. monocytic cells to epithelial cultures induced a robust release of CXCL10 by the epithelial cells. This effect was greatly attenuated by type I interferon receptor blocking antibodies, and could be recapitulated by IFN addition. Conclusions Our data indicate that epithelial CXCL10 release during HRV infection is augmented by a monocytic cell-dependent mechanism involving type I interferon(s). Our findings support a key role for monocytic cells in the amplification of epithelial cell chemokine production during HRV infection, and help explain how an inflammatory milieu is created in the lower airways even in the absence of extensive viral replication and epithelial infection. work with human cells because of the specificity of major group HRV serotypes for human ICAM-1, which is necessary for viral entry [17]. Although recent work has led to the development of a transgenic mouse with a chimeric mouse-human ICAM-1 for the study of major group HRV serotypes [16], most information on these viruses has come from infection of human cells in culture. studies using human airway epithelial cells challenged with HRV demonstrate increased production of inflammatory mediators including interleukins (IL-1, IL-6, CXCL8 (IL-8), IL-11), interferon-, CXCL10 (IP-10), CXCL5 (ENA-78), granulocyte macrophage-colony stimulating factor (GM-CSF), CXCL1 (GRO), and CCL5 (RANTES) [18C22]. Several reports have noted that the Duloxetine early expression of certain cytokines, such as CXCL8, may not be dependent on viral replication [18, 23]. Conversely, other studies have indicated that the secretion of many of these pro-inflammatory cytokines by epithelial cells appears to be dependent on the internalization and replication of viral RNA, as UV-inactivated HRV does not elicit a similarly strong response, whereas transfection of dsRNA does result in robust cytokine release [20C22]. Analysis of biopsies from the epithelium of HRV-infected human subjects, however, reveals an apparent complication in the model wherein epithelial cell infection Duloxetine is necessary for cytokine release. Although the above studies suggest that HRV-stimulated cytokine production by epithelial Duloxetine cells is dependent on the presence of replicative virus, only a very small proportion of cells in primary human cultures [24] or epithelium biopsies from human volunteers appear to be actively infected [25, 26]. Nonetheless, during HRV infection there are marked elevations in the concentrations of numerous inflammatory mediators that are believed to be produced primarily by epithelial cells [9C12]. These observations suggest that uninfected epithelial cells may also be producing pro-inflammatory cytokines/chemokines, possibly as a result of a paracrine stimulus from adjacent airway cells. In contrast to epithelial cells, previous reports indicate that internalization of HRV by monocytic cells (monocytes and alveoloar macrophages) does not result in a productive infection and does not cause cell death [27, 28]. As such, monocytic cells in the airway are poised to Duloxetine respond to the presence of HRV and may act as continuing sentinels during infection. Studies conducted in our laboratory and others have revealed that monocytes/macrophages are a source of immune modulators following HRV challenge, as HRV stimulates monocyte/macrophage production of type I interferons, IL-10, tumor necrosis factor-, CXCL8, CCL2 (MCP-1), and CXCL10 [27C32]. Studies in Rabbit polyclonal to Betatubulin which HRV-induced release of CCL2 and CXCL10 from human blood monocytic cells and human alveolar macrophages were examined in parallel showed a similar cytokine response between the two cell types [29, 32], indicating the use of blood monocytic cells, as a more readily available source of immune cells, can be useful in the study of CCL2 and CXCL10 release in.