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Cyclic AMP synergizes with butyrate in promoting -defensin 9 expression in chickens

Published: October 9, 2018
By: Lakshmi T. Sunkara 1, Xiangfang Zeng 1, Amanda R. Curtis 1, Guolong Zhang 1, 2, 3. / 1 Department of Animal Science, Oklahoma State University, Stillwater, OK 74078, USA; 2 Department of Biochemistry and Molecular Biology, Oklahoma State University, Stillwater, OK 74078, USA; 3 Department of Physiological Sciences, Center for Veterinary Health Sciences, Oklahoma State University, Stillwater, OK 74078, USA.


Host defense peptides (HDP) have both microbicidal and immunomodulatory properties. Specific induction of endogenous HDP synthesis has emerged as a novel approach to antimicrobial therapy. Cyclic adenosine monophosphate (cAMP) and butyrate have been implicated in HDP induction in humans. However, the role of cAMP signaling and the possible interactions between cAMP and butyrate in regulating HDP expression in other species remain unknown. Here we report that activation of cAMP signaling induces HDP gene expression in chickens as exemplified by -defensin 9 (AvBD9). We further showed that, albeit being weak inducers, cAMP agonists synergize strongly with butyrate or butyrate analogs in AvBD9 induction in macrophages and primary jejunal explants. Additionally, oral supplementation of forskolin, an adenylyl cyclase agonist in the form of a Coleus forskohlii extract, was found to induce AvBD9 expression in the crop of chickens. Furthermore, feeding with both forskolin and butyrate showed an obvious synergy in triggering AvBD9 expression in the crop and jejunum of chickens. Surprisingly, inhibition of the MEK-ERK mitogen-activated protein kinase (MAPK) pathway augmented the butyrate-FSK synergy, whereas blocking JNK or p38 MAPK pathway significantly diminished AvBD9 induction in chicken macrophages and jejunal explants in response to butyrate and FSK individually or in combination. Collectively, these results suggest the potential for concomitant use of butyrate and cAMP signaling activators in enhancing HDP expression, innate immunity, and disease resistance in both animals and humans.
Keywords: Host defense peptide, cAMP signaling, Butyrate, Disease resistance, Antibiotic alternative, Chickens.

This abstract was originally published in Molecular Immunology 57 (2014) 171–180. http://dx.doi.org/10.1016/j.molimm.2013.09.003.
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Lakshmi Sunkara
Oklahoma State University
Glenn Zhang
Oklahoma State University
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