Submitted to: Developmental and Comparative Immunology
Publication Type: Peer Reviewed Journal
Publication Acceptance Date: 12/24/2010
Publication Date: 4/1/2011
Publication URL: http://www.sciencedirect.com/science/article/pii/S0145305X10003101
Citation: Chen, H., Lunney, J.K., Cheng, L., Li, X., Cao, J., Zhu, M., Zhao, S. 2011. Porcine S100A8 and S100A9: molecular characterizations and crucial functions in response to Haemophilus parasuis infection. Developmental and Comparative Immunology. 35(4):490-500. Interpretive Summary: This manuscript focuses on the role of 2 important genes, S100A8 (S100 calcium-binding protein A8) and S100A9 (S100 calcium-binding protein A9) and their role in immunity and responses to Haemophilus parasuis (HPS) infection in pigs. It explores the possibility of using S100A8 and S100A9 expression as biomarkers for HPS, a disease which has become an increasing threat to pigs with considerable economic losses. In this manuscript, we present molecular characterization of porcine S100A8 and S100A9 genes, their responses to immunostimulation, and potential functions in resistance to Haemophilus parasuis infection.
Technical Abstract: S100 calcium-binding protein A8 (S100A8) and S100 calcium-binding protein A9 (S100A9) are pivotal mediators of inflammatory and protective anti-infection responses for the mammalian host. In this study, we present the molecular cloning of porcine S100A8 (pS100A8) and porcine S100A9 (pS100A9). Both genes comprise 3 exons and 2 introns and are located on pig chromosome 4q21-q23 (closely linked to SW512). Homology comparison to other mammalian species affirmed that critical functional amino acids for post-transcriptional modification, inflammatory regulation, and formation of heterodimeric complexes exist in pS100A8 and pS100A9. Under normal conditions, both genes are preferentially expressed in porcine immune or immune-related organs, e.g., bone marrow, spleen, lymph nodes, and lung. Upon stimulation in porcine whole blood cultures with LPS or Poly(I:C), they are dramatically induced. Interestingly, the maximum increase of mRNA levels in blood cultures of Meishan pigs are significantly greater than that in Duroc pigs. We previously showed that pS100A8 and pS100A9 mRNA were up-regulated following Haemophilus parasuis (HPS) infection. We herein further confirm their up-regulation at the protein level in multiple HPS infected tissues (spleen, lung and liver). Functional cluster and network analysis based on our previous microarray data discovered that CEBPB may be one of the key transcription factors. A pS100A8/pS100A9-CASP3-SLC1A2 pathway regulating lipid metabolism was found. Both of their pro- and anti-inflammatory functions in response to HPS infection are highlighted.