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Two novel MKKs (MKK4 and MKK7) from Ctenopharyngodon idella are involved in the intestinal immune response to bacterial muramyl dipeptide challenge.
- Source :
-
Developmental and comparative immunology [Dev Comp Immunol] 2019 Apr; Vol. 93, pp. 103-114. Date of Electronic Publication: 2019 Jan 08. - Publication Year :
- 2019
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Abstract
- Mitogen-activated protein kinase kinases (MKKs) are a class of evolutionarily conserved signalling intermediates of the MAPK signalling pathway that can be activated by a diverse range of pathogenic stimuli and are crucial for the regulation of host immune defence. In this study, two fish MKK genes (CiMKK4 and CiMKK7) were first identified and characterized from grass carp (Ctenopharyngodon idella). Similar to other reported MKKs, the present CiMKK4 and CiMKK7 contained a conserved serine/threonine protein kinase (S&#95;TKc) domain and a canonical dual phosphorylation motif. Quantitative real-time PCR results showed that CiMKK4 and CiMKK7 were broadly transcribed in all selected tissues and developmental stages of grass carp. The mRNA expression levels of CiMKK4 and CiMKK7 in the intestine were significantly induced by bacterial muramyl dipeptide (MDP) challenge in a time-dependent manner (P < 0.01). Additionally, the stimulatory effects of bacterial MDP on CiMKK4 and CiMKK7 expression in the intestine were inhibited by the bioactive dipeptide β-alanyl-l-histidine (carnosine) and alanyl-glutamine (Ala-Gln) (P < 0.05). Moreover, overexpression analysis revealed that CiMKK4 and CiMKK7 were localized throughout the entire cell and could significantly enhance AP-1 reporter gene activation in HEK293T cells. Taken together, these results provide the first experimental demonstration that CiMKK4 and CiMKK7 are involved in the intestinal immune response to MDP challenge in C. idella, which may provide new insight into the bacterial-induced intestinal inflammation of bony fishes.<br /> (Copyright © 2019 Elsevier Ltd. All rights reserved.)
- Subjects :
- Amino Acid Sequence
Animals
Base Sequence
Carps microbiology
Cell Line
Fish Diseases immunology
Fish Diseases microbiology
Fish Proteins genetics
HEK293 Cells
Humans
Intestines microbiology
MAP Kinase Kinase 4 genetics
MAP Kinase Kinase 7 genetics
Open Reading Frames genetics
RNA, Messenger genetics
Sequence Analysis, DNA
Signal Transduction immunology
Acetylmuramyl-Alanyl-Isoglutamine immunology
Carps immunology
Intestines immunology
MAP Kinase Kinase 4 metabolism
MAP Kinase Kinase 7 metabolism
Subjects
Details
- Language :
- English
- ISSN :
- 1879-0089
- Volume :
- 93
- Database :
- MEDLINE
- Journal :
- Developmental and comparative immunology
- Publication Type :
- Academic Journal
- Accession number :
- 30633955
- Full Text :
- https://doi.org/10.1016/j.dci.2019.01.001