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Cathelicidin derivative IDR-1018 exhibits anti-protease effects that alleviate Citrobacter rodentium-induced colitis

ABSTRACT: Short, cationic, and amphipathic host defence peptides exhibit a wide range of anti-infective, anti-inflammatory, wound-healing, and antibiofilm activities. A synthetic peptide innate defence regulator (IDR) 1018, derived from the bovine neutrophil bactenecin, has been proposed as a therapeutic candidate for treating bacterial infections due to its immunomodulatory and antibacterial properties. IDR-1018 was examined as a treatment in murine colitis caused by the attaching/effacing enteropathogen, Citrobacter rodentium. IDR-1018, administered intra-peritoneally for three consecutive days after oral challenge with C. rodentium, mitigated microscopic lesions of colitis. Specifically, IDR-1018 reduced fecal protease levels, particularly elastase, by increasing the formation of inhibitory elastase–serpin complexes. IDR-1018 targeted neutrophils, the main effectors in colitis. Human and murine neutrophils stimulated and recruited by IDR-1018 exhibited reduced protease and elastase activity, as well as lower inflammatory cytokine production in response to inflammatory stimulation, showing functional reprogramming toward a less tissue-damaging phenotype. This study reveals a new activity of IDR-1018 in counteracting protease, which correspondingly attenuates C. rodentium colitis.

INSTRUMENT(S):

ORGANISM(S): Mus Musculus (mouse)

TISSUE(S): Colon

SUBMITTER: Daniel Young

LAB HEAD: Antoine Dufour

PROVIDER: PXD076043 | Pride | 2026-04-14

REPOSITORIES: Pride

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			Action	DRS
	2026-3-6_Cobo_CR_peptide.zip	Other
	S19987_202_Cobo_CR_Peptide_1_260228.raw	Raw
	S19988_203_Cobo_CR_Peptide_2_260228.raw	Raw
	S19989_204_Cobo_CR_Peptide_3_260228.raw	Raw
	S19990_205_Cobo_CR_Peptide_4_260228.raw	Raw

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