Melanocortin-derived tripeptide KPV has anti-inflammatory potential in murine models of inflammatory bowel disease

Kannengießer, Klaus; Maaser, Christian; Heidemann, Jan; Luegering, Andreas; Ross, Matthias; Brzoska, Thomas; Böhm, Markus; Luger, Thomas A.; Domschke, Wolfram; Kucharzik, Torsten

doi:10.1002/ibd.20334

Cited by 49 publications

(39 citation statements)

References 37 publications

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“…A total of 1 3 10 6 CD4 + CD25 2 T cells was adoptively transferred i.v. into Rag 2/2 mice (on a C57BL/6 background), which do not develop functional T cells (28,29). The weight of animals was monitored frequently (at least every 2 d) until they lost body weight on consecutive days and colitis was established (30).…”

Section: Syngeneic Cd4mentioning

confidence: 99%

Immune Suppression via Glucocorticoid-Stimulated Monocytes: A Novel Mechanism To Cope with Inflammation

Varga

Ehrchen

Brockhausen

et al. 2014

The Journal of Immunology

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Glucocorticoids (GCs) are used as first-line therapies for generalized suppression of inflammation (e.g., allergies or autoimmune diseases), but their long-term use is limited by severe side effects. Our previous work revealed that GCs induced a stable anti-inflammatory phenotype in monocytes, the GC-stimulated monocytes (GCsMs) that we exploited for targeted GC-mediated therapeutic effects. We demonstrate that GCsMs interact with T cells in suppressing proliferation, as well as cytokine release of CD8+ and, especially, CD4+ T cells in vitro, and that they support generation of Foxp3+ cells. Therefore, we tested their immunosuppressive potential in CD4+ T cell–induced colitis in vivo. We found that injection of GCsMs into mice with severe colitis abolished the inflammation and resulted in significant clinical improvement within a few days. T cells recovered from GCsM-treated mice exhibited reduced secretion of proinflammatory cytokines IFN-γ and IL-17. Furthermore, clusters of Foxp3+ CD4+ T cells were detectable at local sites of inflammation in the colon. Thus, GCsMs are able to modify T cell responses in vitro and in vivo, as well as to downregulate and clinically cure severe T cell–mediated colitis.

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Section: Syngeneic Cd4mentioning

confidence: 99%

Immune Suppression via Glucocorticoid-Stimulated Monocytes: A Novel Mechanism To Cope with Inflammation

Varga

Ehrchen

Brockhausen

et al. 2014

The Journal of Immunology

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“…Over the last four decades a substantial body of evidence has exposed their beneficial effects in models of asthma [42][43][44], inflammatory bowel disease [45][46][47], cardiovascular disease [48][49][50][51][52][53], and neuroprotection [54-56] to name just a few areas.…”

Section: Page 6 Of 39mentioning

confidence: 99%

Melanocortin peptides protect chondrocytes from mechanically induced cartilage injury

Kaneva

Kerrigan

Grieco

et al. 2014

Biochemical Pharmacology

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Conclusion:Melanocortin peptide pre-treatment prevented chondrocyte death following mechanical impact to cartilage and led to a marked reduction of pro-inflammatory cytokines, whilst prompting the production of anti-inflammatory/pro-resolving cytokine IL-10.Development of small molecule agonists towards melanocortin receptors could thus be a viable approach for preventing chondrocyte inflammation and death within cartilage and represent an alternative approach for the treatment of osteoarthritis.

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“…10 The ␣-MSH-derived C-terminal tripeptide KPV is anti-inflammatory in crystal-induced peritonitis 11 and in two models of inflammatory bowel disease. 12 New therapeutic strategies based on this line of research have also explored ␣-MSH gene therapy in a model of thioacetamide-induced hepatic fibrosis, 13 affording tissue protection, and the oral administration of recombinant Lactobacillus casei, which secretes ␣-MSH, which reduced body weight loss, survival, clinical score, and myeloperoxidase (MPO) activity in a model of ulcerative colitis. 14 In in vitro settings, MC agonists display anticytokine effects on macrophages 15 and can induce the development of cytotoxic CD8 ϩ T cells 16 and CD25 ϩ CD4 ϩ regulatory T cells.…”

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confidence: 99%

The Melanocortin Agonist AP214 Exerts Anti-Inflammatory and Proresolving Properties

Montero‐Melendez

Patel

Seed

et al. 2011

The American Journal of Pathology

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Synthetic and natural melanocortin (MC) peptides afford inhibitory properties in inflammation and tissue injury, but characterization of receptor involvement is still elusive. We used the agonist AP214 to test MC-dependent anti-inflammatory effects. In zymosan peritonitis, treatment of mice with AP214 (400 to 800 g/kg) inhibited cell infiltration, an effect retained in MC receptor type 1, or MC 1 , mutant mice but lost in MC 3 null mice. In vitro, cytokine release from zymosan-stimulated macrophages was affected by AP214, with approximately 80%, 30%, and 40% reduction in IL-1␤, tumor necrosis factor-␣, and IL-6, respectively. Inhibition of IL-1␤ release was retained in MC 1 mutant cells but was lost in MC 3 null cells. Furthermore, AP214 augmented uptake of zymosan particles and human apoptotic neutrophils by wild-type macrophages: this proresolving property was lost in MC 3 null macrophages. AP214 displayed its pro-efferocytotic effect also in vivo.

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Melanocortin-derived tripeptide KPV has anti-inflammatory potential in murine models of inflammatory bowel disease

Abstract: The melanocortin-derived tripeptide KPV showed significant anti-inflammatory effects in 2 murine models of colitis. These effects seem to be at least partially independent of MC1R signaling. In conclusion, our data suggest KPV as an interesting therapeutic option for the treatment of IBD.

Cited by 49 publications

References 37 publications

Immune Suppression via Glucocorticoid-Stimulated Monocytes: A Novel Mechanism To Cope with Inflammation

Immune Suppression via Glucocorticoid-Stimulated Monocytes: A Novel Mechanism To Cope with Inflammation

Melanocortin peptides protect chondrocytes from mechanically induced cartilage injury

The Melanocortin Agonist AP214 Exerts Anti-Inflammatory and Proresolving Properties

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