Cyclic AMP synergizes with butyrate in promoting ß-defensin 9 expression in chickens.
Mol Immunol
; 57(2): 171-80, 2014 Feb.
Article
em En
| MEDLINE
| ID: mdl-24141182
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 ß-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.
Palavras-chave
2',5'-dideoxyadenosine; AP-1; Antibiotic alternative; AvBD9; BZB; Butyrate; CF; CRE; CRE-binding protein; CREB; CT; Chickens; Coleus forskohlii; DB-cAMP; DDA; Disease resistance; FSK; GAPDH; GTB; HBD1; HDACi; HDP; Host defense peptide; ICER; MAPK; PT; VDR; VDR response element; VRE; activator protein-1; avian ß-defensin 9; benzyl butyrate; cAMP; cAMP response element; cAMP signaling; cholera toxin; cyclic adenosine monophosphate; dibutyryl-cAMP; forskolin; glyceraldehyde-3-phosphate dehydrogenase; glyceryl tributyrate; histone deacetylase inhibitor; host defense peptide; human ß-defensin 1; inducible cAMP early repressor; mitogen-activated protein kinase; pertussis toxin; vitamin D receptor
Texto completo:
1
Base de dados:
MEDLINE
Assunto principal:
Butiratos
/
AMP Cíclico
/
Beta-Defensinas
/
Imunidade Inata
Limite:
Animals
Idioma:
En
Revista:
Mol Immunol
Ano de publicação:
2014
Tipo de documento:
Article
País de afiliação:
Estados Unidos