PIM2 Induced COX-2 and MMP-9 expression in macrophages requires PI3K and Notch1 signaling.
Activation of inflammatory immune responses during granuloma formation by the host upon infection of mycobacteria is one of the crucial steps that is often associated with tissue remodeling and breakdown of the extracellular matrix. In these complex processes, cyclooxygenase-2 (COX-2) plays a major...
| Main Authors: | , , , , , |
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| Format: | Article |
| Language: | English |
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Public Library of Science (PLoS)
2009-01-01
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| Series: | PLoS ONE |
| Online Access: | http://europepmc.org/articles/PMC2654112?pdf=render |
| _version_ | 1818586302814093312 |
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| author | Kushagra Bansal Nisha Kapoor Yeddula Narayana Germain Puzo Martine Gilleron Kithiganahalli Narayanaswamy Balaji |
| author_facet | Kushagra Bansal Nisha Kapoor Yeddula Narayana Germain Puzo Martine Gilleron Kithiganahalli Narayanaswamy Balaji |
| author_sort | Kushagra Bansal |
| collection | DOAJ |
| description | Activation of inflammatory immune responses during granuloma formation by the host upon infection of mycobacteria is one of the crucial steps that is often associated with tissue remodeling and breakdown of the extracellular matrix. In these complex processes, cyclooxygenase-2 (COX-2) plays a major role in chronic inflammation and matrix metalloproteinase-9 (MMP-9) significantly in tissue remodeling. In this study, we investigated the molecular mechanisms underlying Phosphatidyl-myo-inositol dimannosides (PIM2), an integral component of the mycobacterial envelope, triggered COX-2 and MMP-9 expression in macrophages. PIM2 triggers the activation of Phosphoinositide-3 Kinase (PI3K) and Notch1 signaling leading to COX-2 and MMP-9 expression in a Toll-like receptor 2 (TLR2)-MyD88 dependent manner. Notch1 signaling perturbations data demonstrate the involvement of the cross-talk with members of PI3K and Mitogen activated protein kinase pathway. Enforced expression of the cleaved Notch1 in macrophages induces the expression of COX-2 and MMP-9. PIM2 triggered significant p65 nuclear factor -kappaB (NF-kappaB) nuclear translocation that was dependent on activation of PI3K or Notch1 signaling. Furthermore, COX-2 and MMP-9 expression requires Notch1 mediated recruitment of Suppressor of Hairless (CSL) and NF-kappaB to respective promoters. Inhibition of PIM2 induced COX-2 resulted in marked reduction in MMP-9 expression clearly implicating the role of COX-2 dependent signaling events in driving the MMP-9 expression. Taken together, these data implicate PI3K and Notch1 signaling as obligatory early proximal signaling events during PIM2 induced COX-2 and MMP-9 expression in macrophages. |
| first_indexed | 2024-12-16T08:50:49Z |
| format | Article |
| id | doaj.art-8fc04635410a4ce48e0d7a4368705552 |
| institution | Directory Open Access Journal |
| issn | 1932-6203 |
| language | English |
| last_indexed | 2024-12-16T08:50:49Z |
| publishDate | 2009-01-01 |
| publisher | Public Library of Science (PLoS) |
| record_format | Article |
| series | PLoS ONE |
| spelling | doaj.art-8fc04635410a4ce48e0d7a43687055522022-12-21T22:37:27ZengPublic Library of Science (PLoS)PLoS ONE1932-62032009-01-0143e491110.1371/journal.pone.0004911PIM2 Induced COX-2 and MMP-9 expression in macrophages requires PI3K and Notch1 signaling.Kushagra BansalNisha KapoorYeddula NarayanaGermain PuzoMartine GilleronKithiganahalli Narayanaswamy BalajiActivation of inflammatory immune responses during granuloma formation by the host upon infection of mycobacteria is one of the crucial steps that is often associated with tissue remodeling and breakdown of the extracellular matrix. In these complex processes, cyclooxygenase-2 (COX-2) plays a major role in chronic inflammation and matrix metalloproteinase-9 (MMP-9) significantly in tissue remodeling. In this study, we investigated the molecular mechanisms underlying Phosphatidyl-myo-inositol dimannosides (PIM2), an integral component of the mycobacterial envelope, triggered COX-2 and MMP-9 expression in macrophages. PIM2 triggers the activation of Phosphoinositide-3 Kinase (PI3K) and Notch1 signaling leading to COX-2 and MMP-9 expression in a Toll-like receptor 2 (TLR2)-MyD88 dependent manner. Notch1 signaling perturbations data demonstrate the involvement of the cross-talk with members of PI3K and Mitogen activated protein kinase pathway. Enforced expression of the cleaved Notch1 in macrophages induces the expression of COX-2 and MMP-9. PIM2 triggered significant p65 nuclear factor -kappaB (NF-kappaB) nuclear translocation that was dependent on activation of PI3K or Notch1 signaling. Furthermore, COX-2 and MMP-9 expression requires Notch1 mediated recruitment of Suppressor of Hairless (CSL) and NF-kappaB to respective promoters. Inhibition of PIM2 induced COX-2 resulted in marked reduction in MMP-9 expression clearly implicating the role of COX-2 dependent signaling events in driving the MMP-9 expression. Taken together, these data implicate PI3K and Notch1 signaling as obligatory early proximal signaling events during PIM2 induced COX-2 and MMP-9 expression in macrophages.http://europepmc.org/articles/PMC2654112?pdf=render |
| spellingShingle | Kushagra Bansal Nisha Kapoor Yeddula Narayana Germain Puzo Martine Gilleron Kithiganahalli Narayanaswamy Balaji PIM2 Induced COX-2 and MMP-9 expression in macrophages requires PI3K and Notch1 signaling. PLoS ONE |
| title | PIM2 Induced COX-2 and MMP-9 expression in macrophages requires PI3K and Notch1 signaling. |
| title_full | PIM2 Induced COX-2 and MMP-9 expression in macrophages requires PI3K and Notch1 signaling. |
| title_fullStr | PIM2 Induced COX-2 and MMP-9 expression in macrophages requires PI3K and Notch1 signaling. |
| title_full_unstemmed | PIM2 Induced COX-2 and MMP-9 expression in macrophages requires PI3K and Notch1 signaling. |
| title_short | PIM2 Induced COX-2 and MMP-9 expression in macrophages requires PI3K and Notch1 signaling. |
| title_sort | pim2 induced cox 2 and mmp 9 expression in macrophages requires pi3k and notch1 signaling |
| url | http://europepmc.org/articles/PMC2654112?pdf=render |
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