1. Antileishmanial Activity of Cathelicidin and its Modulation by Leishmania donovani in a cAMP Response Element Modulator-Dependent Manner in Infection.
- Author
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Roy, Shalini, Roy, Souravi, Banerjee, Madhurima, Madbhagat, Pratibha, Chande, Ajit, and Ukil, Anindita
- Subjects
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TRANSCRIPTION factors , *VISCERAL leishmaniasis , *LEISHMANIA donovani , *ANTIMICROBIAL peptides , *DRUG resistance - Abstract
Concerns regarding toxicity and resistance of current drugs in visceral leishmaniasis have been reported. Antimicrobial peptides are considered to be promising candidates and among them human cathelicidin hCAP18/LL-37 showed significant parasite killing on drug-sensitive and resistant Leishmania promastigotes, in addition to its apoptosis-inducing role. Administration of hCAP18/LL-37 to infected macrophages also decreased parasite survival and increased the host favorable cytokine interleukin 12. However, 1,25-dihydroxyvitamin D3 (vitamin D3)-induced endogenous hCAP18/LL-37 production was hampered in infected THP-1 cells. Infection also suppressed the vitamin D3 receptor (VDR), transcription factor of hCAP18/LL-37. cAMP response element modulator (CREM), the repressor of VDR, was induced in infection, resulting in suppression of both VDR and cathelicidin expression. PGE2/cAMP/PKA axis was found to regulate CREM induction during infection and silencing CREM in infected cells and BALB/c mice led to decreased parasite survival. This study documents the antileishmanial potential of cathelicidin and further identifies CREM as a repressor of cathelicidin in Leishmania infection. [ABSTRACT FROM AUTHOR]
- Published
- 2024
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