Loading...
Please wait, while we are loading the content...
Similar Documents
Exogenous ghrelin modulates release of pro-inflammatory and anti-inflammatory cytokines in LPS-stimulated macrophages through distinct signaling pathways.
| Content Provider | Semantic Scholar |
|---|---|
| Author | Waseem, Talat Duxbury, Mark S. Ito, Hiromichi Ashley, Stanley W. Robinson, Malcolm K. |
| Copyright Year | 2008 |
| Abstract | BACKGROUND Ghrelin, an orexigenic 28-amino-acid peptide, has been studied primarily in relation to the control of appetite and fat metabolism. In addition to these well-known functions, ghrelin, and its target receptors, growth hormone secretagogue receptors (GHS-Rs), have been localized to neutrophils, lymphocytes, and macrophages, which suggests that ghrelin may be involved in immune modulation. METHODS To assess the therapeutic role of ghrelin in production of pro-inflammatory and anti-inflammatory cytokines, the effects of exogenous ghrelin administration on the regulation of cytokine release in lipopolysaccharide (LPS)-activated murine RAW 264.7 macrophages were analyzed. RESULTS Ghrelin and GHS-Rs are expressed in murine macrophages. In addition, exogenous ghrelin inhibited the production of pro-inflammatory cytokines IL-1beta and TNF-alpha in LPS-stimulated murine macrophages in a dose dependent and time-dependent fashion. Exogenous ghrelin pretreatment resulted in a decrease in LPS-induced NFkappaB activation and was presumably the reason for this ghrelin-mediated effect. In contrast to these findings, exogenous ghrelin significantly augmented the release of the anti-inflammatory cytokine IL-10 in a dose-dependent and time-dependent fashion from LPS-stimulated murine macrophages. Ghrelin administration enhanced activation of p38 MAPK, which is known to control the release of IL-10 in macrophages independent of the NFkappaB pathway. These effects of ghrelin on both pro-inflammatory and anti-inflammatory cytokines were offset when a specific GHS-R receptor antagonist was added to the culture media. CONCLUSIONS These data suggest that ghrelin has potent anti-inflammatory properties through modulation of secretion of both pro-inflammatory and anti-inflammatory cytokines from LPS-stimulated macrophages through distinct signaling cascades. Therapeutic utility of ghrelin to control, modulate, or treat pathologic inflammatory conditions like endotoxemic shock and ulcerative colitis requires additional investigation. |
| File Format | PDF HTM / HTML |
| DOI | 10.1016/j.surg.2007.09.039 |
| PubMed reference number | 18291254 |
| Journal | Medline |
| Volume Number | 143 |
| Issue Number | 3 |
| Alternate Webpage(s) | https://www.research.ed.ac.uk/portal/files/10650143/Exogenous_ghrelin_modulates_release_of_pro_inflammatory_and_anti_inflammatory_cytokines_in_LPS_stimulated_macrophages_through_distinct_signaling_pathways.pdf |
| Alternate Webpage(s) | https://doi.org/10.1016/j.surg.2007.09.039 |
| Journal | Surgery |
| Language | English |
| Access Restriction | Open |
| Content Type | Text |
| Resource Type | Article |
