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Abstract
Thanthrige Thiunuwan Priyathilakaa, S.D.N.K. Bathigeb, Seongdo Leec,d, Hyerim Yangc, Taehyuk Jeongc,d, Sukkyoung Leec,d, Jehee Leec,d,*
aDepartment of Pathology and Laboratory Medicine, University of Wisconsin-Madison, Madison, WI, 53705, USA
bSri Lanka Institute of Nanotechnology (SLINTEC), Nanotechnology and Science Park, Mahenwatta, Pitipana, Homagama, Sri Lanka
cDepartment of Marine Life Sciences & Fish Vaccine Research Center, Jeju National University, Jeju Self-Governing Province, 63243, Republic of Korea
dMarine Science Institute, Jeju National University, Jeju Self-Governing Province, 63333, Republic of Korea
*Corresponding author
Abstract
The IκB kinases (IKK) are large multiprotein complexes that regulate the activation of the transcription factor NF-κB and are involved in a diverse range of biological processes, including innate immunity, inflammation, and development. To explore the potential roles of invertebrate IKKs on immunity, three IKK encoding genes have been identified from molluscan species disk abalone and designed as AbIKK1, AbIKK2 and AbIKK3 at the transcriptional level. Coding sequences of AbIKK1, AbIKK2 and AbIKK3 encode the peptides of 746, 751 and 713 amino acids with the predicted molecular mass of 86.16, 86.12 and 81.88 kDa respectively. All three AbIKKs were found to share conserved IKK family features including the kinase superfamily domain (KD), ubiquitin-like domain (ULD), and α-helical scaffold/dimerization domain (SDD), similar to their mammalian counterparts. Under normal physiological conditions, AbIKKs were ubiquitously detected in six different tissues, with the highest abundance in the digestive tract and gills. Temporal transcriptional profiles of abalone hemocytes revealed the induction of AbIKK1, AbIKK2, and AbIKK3 expression following exposure to Gram-negative (Vibrio parahemolyticus) and Gram-positive (Listeria monocytogenes) bacteria, viruses (viral hemorrhagic septicemia virus, VHSV), LPS, or poly I:C. The overexpression of AbIKKs in HEK293T or RAW264.7 murine macrophage cells induced NF-κB promoter activation independent of stimulation by TNF-α or LPS. Moreover, iNOS and COX2 expression was induced in AbIKK transfected RAW264.7 murine macrophage cells and the induced state was maintained post-LPS treatment. Furthermore, mRNA levels of three selected cytokine-encoding genes (IL-1β, IL-6, and TNF-α) were found to be elevated in abalone IKK1-, IKK2-, and IKK3-overexpressed RAW264.7 murine macrophage cells, both with and without LPS exposure. Overall, our findings demonstrated that AbIKKs identified in this study were positively involved in eliciting innate immune responses in abalone. In addition, the data revealed the presence of an evolutionarily conserved signaling mechanism for IKK mediated NF-κB activation in mollusks.
Keywords
Haliotis discus discus; IKK; NF-κB activation; Innate immune responses
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