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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

Productions of pro-inflammatory cytokines and expressions of TLRs. Colons from mock or DSS-treated WT and GHSR−/− mice were collected, and the production of pro-inflammatory cytokines TNF and IL-6 were detected by ELISA. The final results were expressed as the radio of cytokine concentration to total protein content (A). Moreover, the RNA levels of TNF, IL-1β, IL-6, M-CSF, GM-CSF and IFN-γ were also examined in colons (B). Finally, the innate immune receptors of TLR-2 and TLR-4 were quantified in colon and MLN as well respectively (C). Each bar represents the mean ± SEM; *p < 0.05, **p < 0.01, and ***p < 0.005.
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Fig4: Productions of pro-inflammatory cytokines and expressions of TLRs. Colons from mock or DSS-treated WT and GHSR−/− mice were collected, and the production of pro-inflammatory cytokines TNF and IL-6 were detected by ELISA. The final results were expressed as the radio of cytokine concentration to total protein content (A). Moreover, the RNA levels of TNF, IL-1β, IL-6, M-CSF, GM-CSF and IFN-γ were also examined in colons (B). Finally, the innate immune receptors of TLR-2 and TLR-4 were quantified in colon and MLN as well respectively (C). Each bar represents the mean ± SEM; *p < 0.05, **p < 0.01, and ***p < 0.005.

Mentions: There was constitutive level of colonic TNF from both GHSR−/− and WT mice without significant difference, as measured by tissue ELISA. Colonic TNF was significantly upregulated in DSS-challenged WT mice (~2 fold, p < 0.01), but not GHSR−/− mice, compared to mock treated mice. Furthermore, colonic TNF was significantly higher in DSS-challenged WT compared to that of GHSR−/− mice (p < 0.05) (Figure 4A). A similar pattern was observed in colonic IL-6 production, which was markedly increased in DSS-challenged WT mice compared to mock treated WT mice (~2 fold, p < 0.05) or DSS-treated GHSR−/− mice (~2 fold, p < 0.05) (Figure 4A).Figure 4


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)

Productions of pro-inflammatory cytokines and expressions of TLRs. Colons from mock or DSS-treated WT and GHSR−/− mice were collected, and the production of pro-inflammatory cytokines TNF and IL-6 were detected by ELISA. The final results were expressed as the radio of cytokine concentration to total protein content (A). Moreover, the RNA levels of TNF, IL-1β, IL-6, M-CSF, GM-CSF and IFN-γ were also examined in colons (B). Finally, the innate immune receptors of TLR-2 and TLR-4 were quantified in colon and MLN as well respectively (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

Fig4: Productions of pro-inflammatory cytokines and expressions of TLRs. Colons from mock or DSS-treated WT and GHSR−/− mice were collected, and the production of pro-inflammatory cytokines TNF and IL-6 were detected by ELISA. The final results were expressed as the radio of cytokine concentration to total protein content (A). Moreover, the RNA levels of TNF, IL-1β, IL-6, M-CSF, GM-CSF and IFN-γ were also examined in colons (B). Finally, the innate immune receptors of TLR-2 and TLR-4 were quantified in colon and MLN as well respectively (C). Each bar represents the mean ± SEM; *p < 0.05, **p < 0.01, and ***p < 0.005.
Mentions: There was constitutive level of colonic TNF from both GHSR−/− and WT mice without significant difference, as measured by tissue ELISA. Colonic TNF was significantly upregulated in DSS-challenged WT mice (~2 fold, p < 0.01), but not GHSR−/− mice, compared to mock treated mice. Furthermore, colonic TNF was significantly higher in DSS-challenged WT compared to that of GHSR−/− mice (p < 0.05) (Figure 4A). A similar pattern was observed in colonic IL-6 production, which was markedly increased in DSS-challenged WT mice compared to mock treated WT mice (~2 fold, p < 0.05) or DSS-treated GHSR−/− mice (~2 fold, p < 0.05) (Figure 4A).Figure 4

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