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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

Histopathological analysis for the acute DSS-induced colitis in WT and GHSR−/−mice. Colons from DSS-treated WT and GHSR−/− mice were collected and prepared for H&E staining. The mucosal damage/inflammation in ascending (A), transverse (B) and descending portions (C) were estimated using a histological scoring system. Each bar represents the mean ± SEM; NS: no significance, * p < 0.05 and *** p < 0.005.
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Fig3: Histopathological analysis for the acute DSS-induced colitis in WT and GHSR−/−mice. Colons from DSS-treated WT and GHSR−/− mice were collected and prepared for H&E staining. The mucosal damage/inflammation in ascending (A), transverse (B) and descending portions (C) were estimated using a histological scoring system. Each bar represents the mean ± SEM; NS: no significance, * p < 0.05 and *** p < 0.005.

Mentions: Histopathology score, including intestinal inflammation and crypt damage, was applied to determine the severity of colitis, as described [13]. There was no obvious colonic damage from both GHSR−/− and WT mice without challenge. Severe inflammation was observed in the colons from both GHSR−/− and WT mice following 7 days DSS treatment, showing epithelial ulceration, crypt damage, goblet cell loss and infiltration of inflammatory cells. Additionally, in agreement with previous studies [13], the damage/inflammation in transverse/descending colon (Figure 3A, B) was much more severe than had occurred in the ascending colon (Figure 3C).Figure 3


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)

Histopathological analysis for the acute DSS-induced colitis in WT and GHSR−/−mice. Colons from DSS-treated WT and GHSR−/− mice were collected and prepared for H&E staining. The mucosal damage/inflammation in ascending (A), transverse (B) and descending portions (C) were estimated using a histological scoring system. Each bar represents the mean ± SEM; NS: no significance, * p < 0.05 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

Fig3: Histopathological analysis for the acute DSS-induced colitis in WT and GHSR−/−mice. Colons from DSS-treated WT and GHSR−/− mice were collected and prepared for H&E staining. The mucosal damage/inflammation in ascending (A), transverse (B) and descending portions (C) were estimated using a histological scoring system. Each bar represents the mean ± SEM; NS: no significance, * p < 0.05 and *** p < 0.005.
Mentions: Histopathology score, including intestinal inflammation and crypt damage, was applied to determine the severity of colitis, as described [13]. There was no obvious colonic damage from both GHSR−/− and WT mice without challenge. Severe inflammation was observed in the colons from both GHSR−/− and WT mice following 7 days DSS treatment, showing epithelial ulceration, crypt damage, goblet cell loss and infiltration of inflammatory cells. Additionally, in agreement with previous studies [13], the damage/inflammation in transverse/descending colon (Figure 3A, B) was much more severe than had occurred in the ascending colon (Figure 3C).Figure 3

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