Abstract
BackgroundInterferons play a critical role in regulating both the innate and adaptive immune responses. Previous reports have shown increased levels of IFN-γ, IFN-γ-inducing IL-12 and IFN-γ-inducible chemokine IP-10 in patients with chronic obstructive pulmonary disease (COPD).MethodsThe present study focuses on the regulation of the IP-10 secretion in co-cultures of lung epithelial cells and peripheral blood mononuclear cells (PBMCs).ResultsNo IP-10 secretion was detected in cells cultured alone, whereas a significant increase in IP-10 levels was observed in epithelial cell/PBMC co-cultures. Furthermore, the results show that interactions between lung epithelial cells, lymphocytes and monocytes are needed for basal IP-10 secretion. Interestingly, we have also shown that incubation with IL-12 can induce an IFN-γ independent increase in IP-10 levels in co-cultures. Furthermore, inhibition studies supported the suggestion that different intracellular pathways are responsible of IFN-γ and IL-12 mediated IP-10 secretion.ConclusionThese studies demonstrate a novel diversity in IFN-γ/IL-12 pathways, showing that the IP-10 expression in co-cultures is regulated by multiple factors, such as intercellular interactions in addition to IFN-γ and IL-12 levels. These results may be valuable in designing novel strategies to antagonize IP-10 mediated immunological reactions and chemotactic effects on T cells.
Highlights
Interferons play a critical role in regulating both the innate and adaptive immune responses
Basal and IFN-γ mediated inducible protein 10 (IP-10) secretion from peripheral blood mononuclear cells (PBMCs)/lung epithelial cell co-cultures IP-10 levels in cell culture medium collected after 18 hours from PBMCs, Calu-3, A549 and PBMC/lung epithelial cell co-cultures were measured with ELISA
Very little secretion of IP-10 was detected from unstimulated PBMCs and lung epithelial cell lines (Figure 1. and 2.)
Summary
Interferons play a critical role in regulating both the innate and adaptive immune responses. Previous reports have shown increased levels of IFN-γ, IFN-γ-inducing IL-12 and IFN-γinducible chemokine IP-10 in patients with chronic obstructive pulmonary disease (COPD). Mediators, and proteases are involved in the pathophysiology of COPD. It is characterized by chronic inflammation primarily in the small airways and lung parenchyma, with increased numbers of macrophages, neutrophils and T lymphocytes in comparison to healthy controls [1]. A bias towards a Th1 cell profile has been hypothesized in COPD, with Th1/T cytotoxic 1 (Tc1) pattern and increased Th1 cytokine levels [1]. Th1 cells secrete IL-2, IL-12, and IFN-γ, which has been shown to regulate Th mediated immune and allergic responses by inducing Th1 differentiation.
Sign-in/Register to view highlights & summary Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
