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Growth hormone secretagogue receptor is important in the development of experimental colitis.

Liu ZZ, Wang WG, Li Q, Tang M, Li J, Wu WT, Wan YH, Wang ZG, Bao SS, Fei J - Cell Biosci (2015)

Bottom Line: This is consistent with the observation of less colonic macrophage infiltration and TLRs expression from DSS-treated GHSR(-/-) mice compared to WT mice (P < 0.05).Furthermore, there was significantly reduced pro-inflammatory cytokines in LPS-stimulated macrophages in vitro from GHSR(-/-) mice than WT mice (P < 0.05).Moreover, D-lys(3)-GHRP6 (a GHSR antagonist) reduced LPS-induced macrophage pro-inflammatory cytokines from WT mice in vitro.

View Article: PubMed Central - PubMed

Affiliation: School of Life Science and Technology, Tongji University, Shanghai, 200092 China.

ABSTRACT

Background: Growth hormone secretagogue receptor (GHSR) and its ligand, ghrelin, are important modulators in weight control and energy homeostasis. Recently, ghrelin is also involved in experimental colitis, but the role of GHSR in the development of colitis is unclear. The aim was to examine the underlying mechanism of GHSR in IBD development.

Methods: The temporal expression of GHSR/ghrelin was determined in dextran sulphate sodium (DSS) induced colitis in Wt mice. The severity of DSS induced colitis from GHSR(-/-) and WT mice was compared at clinical/pathological levels. Furthermore, the function of macrophages was evaluated in vivo and in vitro.

Results: Lack of GHSR attenuated colitis significantly at the clinical and pathological levels with reduced colonic pro-inflammatory cytokines (P < 0.05). This is consistent with the observation of less colonic macrophage infiltration and TLRs expression from DSS-treated GHSR(-/-) mice compared to WT mice (P < 0.05). Furthermore, there was significantly reduced pro-inflammatory cytokines in LPS-stimulated macrophages in vitro from GHSR(-/-) mice than WT mice (P < 0.05). Moreover, D-lys(3)-GHRP6 (a GHSR antagonist) reduced LPS-induced macrophage pro-inflammatory cytokines from WT mice in vitro.

Conclusions: GHSR contributes to development of acute DSS-induced colitis, likely via elevated pro-inflammatory cytokines and activation of macrophages. These data suggest GHSR as a potential therapeutic target for IBD.

No MeSH data available.


Related in: MedlinePlus

Infiltration of macrophages in DSS-treated WT and GHSR−/−colons. Colonic infiltrating macrophages were examined by immunohistochemical staining of F4/80. More F4/80+ cells were observed in the submucosal region of inflamed WT colon (A) than GHSR−/−(B). In addition, the numbers F4/80+ cells in the mucosal and submucosal layer were counted, and the final results were showed as numbers of F4/80+ cells in per mm2 mucosa (C). Each bar represents the mean ± SEM; *p < 0.05, **p < 0.01, and ***p < 0.005.
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Fig5: Infiltration of macrophages in DSS-treated WT and GHSR−/−colons. Colonic infiltrating macrophages were examined by immunohistochemical staining of F4/80. More F4/80+ cells were observed in the submucosal region of inflamed WT colon (A) than GHSR−/−(B). In addition, the numbers F4/80+ cells in the mucosal and submucosal layer were counted, and the final results were showed as numbers of F4/80+ cells in per mm2 mucosa (C). Each bar represents the mean ± SEM; *p < 0.05, **p < 0.01, and ***p < 0.005.

Mentions: There was constitutive level of macrophages (F4/80+ cells) in the lamina propria from GHSR−/− and WT mice without significant difference (Figure 5A and B). Infiltrating macrophages were recruited substantially in the inflamed colon following 7 days DSS challenge from both GHSR−/− and WT mice. Compared to unchallenged, there was a ~5 or ~9 fold increase of colonic F4/80+ cell infiltration in GHSR−/− (p < 0.01), or WT (p < 0.005), respectively. The level of infiltrating colonic macrophages was ~2 fold higher in DSS-treated WT mice compared to GHSR−/− mice at 7 days treatment.Figure 5


Growth hormone secretagogue receptor is important in the development of experimental colitis.

Liu ZZ, Wang WG, Li Q, Tang M, Li J, Wu WT, Wan YH, Wang ZG, Bao SS, Fei J - Cell Biosci (2015)

Infiltration of macrophages in DSS-treated WT and GHSR−/−colons. Colonic infiltrating macrophages were examined by immunohistochemical staining of F4/80. More F4/80+ cells were observed in the submucosal region of inflamed WT colon (A) than GHSR−/−(B). In addition, the numbers F4/80+ cells in the mucosal and submucosal layer were counted, and the final results were showed as numbers of F4/80+ cells in per mm2 mucosa (C). Each bar represents the mean ± SEM; *p < 0.05, **p < 0.01, and ***p < 0.005.
© Copyright Policy - open-access
Related In: Results  -  Collection

License 1 - License 2
Show All Figures
getmorefigures.php?uid=PMC4377856&req=5

Fig5: Infiltration of macrophages in DSS-treated WT and GHSR−/−colons. Colonic infiltrating macrophages were examined by immunohistochemical staining of F4/80. More F4/80+ cells were observed in the submucosal region of inflamed WT colon (A) than GHSR−/−(B). In addition, the numbers F4/80+ cells in the mucosal and submucosal layer were counted, and the final results were showed as numbers of F4/80+ cells in per mm2 mucosa (C). Each bar represents the mean ± SEM; *p < 0.05, **p < 0.01, and ***p < 0.005.
Mentions: There was constitutive level of macrophages (F4/80+ cells) in the lamina propria from GHSR−/− and WT mice without significant difference (Figure 5A and B). Infiltrating macrophages were recruited substantially in the inflamed colon following 7 days DSS challenge from both GHSR−/− and WT mice. Compared to unchallenged, there was a ~5 or ~9 fold increase of colonic F4/80+ cell infiltration in GHSR−/− (p < 0.01), or WT (p < 0.005), respectively. The level of infiltrating colonic macrophages was ~2 fold higher in DSS-treated WT mice compared to GHSR−/− mice at 7 days treatment.Figure 5

Bottom Line: This is consistent with the observation of less colonic macrophage infiltration and TLRs expression from DSS-treated GHSR(-/-) mice compared to WT mice (P < 0.05).Furthermore, there was significantly reduced pro-inflammatory cytokines in LPS-stimulated macrophages in vitro from GHSR(-/-) mice than WT mice (P < 0.05).Moreover, D-lys(3)-GHRP6 (a GHSR antagonist) reduced LPS-induced macrophage pro-inflammatory cytokines from WT mice in vitro.

View Article: PubMed Central - PubMed

Affiliation: School of Life Science and Technology, Tongji University, Shanghai, 200092 China.

ABSTRACT

Background: Growth hormone secretagogue receptor (GHSR) and its ligand, ghrelin, are important modulators in weight control and energy homeostasis. Recently, ghrelin is also involved in experimental colitis, but the role of GHSR in the development of colitis is unclear. The aim was to examine the underlying mechanism of GHSR in IBD development.

Methods: The temporal expression of GHSR/ghrelin was determined in dextran sulphate sodium (DSS) induced colitis in Wt mice. The severity of DSS induced colitis from GHSR(-/-) and WT mice was compared at clinical/pathological levels. Furthermore, the function of macrophages was evaluated in vivo and in vitro.

Results: Lack of GHSR attenuated colitis significantly at the clinical and pathological levels with reduced colonic pro-inflammatory cytokines (P < 0.05). This is consistent with the observation of less colonic macrophage infiltration and TLRs expression from DSS-treated GHSR(-/-) mice compared to WT mice (P < 0.05). Furthermore, there was significantly reduced pro-inflammatory cytokines in LPS-stimulated macrophages in vitro from GHSR(-/-) mice than WT mice (P < 0.05). Moreover, D-lys(3)-GHRP6 (a GHSR antagonist) reduced LPS-induced macrophage pro-inflammatory cytokines from WT mice in vitro.

Conclusions: GHSR contributes to development of acute DSS-induced colitis, likely via elevated pro-inflammatory cytokines and activation of macrophages. These data suggest GHSR as a potential therapeutic target for IBD.

No MeSH data available.


Related in: MedlinePlus