Expression of mRNA of chemokines and chemokine receptors and cytokines amount in the blood of healthy volunteers

Kirill Sysoev

Federal Center of Molecular Medicine, I.P. Pavlov State Medical University, St.-Petersbourg, Russia.

DOI: 10.4236/abb.2013.42029                

Abstract

Background: Chemokines are small proteins that activate immune system in normal and pathological conditions. The induction of chemotaxis is a well-established role of chemokines. Moreover chemokines are important mediators of angiogenesis, implantation of fetus, and maturation of immune cells. In human body many types of cells express chemokines and cytokines at level of gene and protein. In blood cells chemokine and chemokine receptors mRNA level is a one of crucial points of chemokine system condition. The aim of the study was to evaluate the relationship between plasma concentration of cyto- kines and chemokines/chemokine receptors mRNA level in blood of healthy volunteers. Results: Gene expression of eotaxin, eotaxin-2, IL-8, MIP-1α, MIP- 1β, RANTES, CCR1, CCR3, CCR5, CXCR1, and CXCR2 was measured in peripheral blood cells, as well as the concentration of IL-1β, IL-1ra, IL-2, IL-4, IL-5, IL-6, IL-7, IL-8, IL-9, IL-10, IL-12 (p70), IL-13, IL-15, IL-17, eotaxin, FGF-2, G-CSF, GM-CSF, IFN-γ, IP-10, MCP-1, MIP-1α, MIP-1β, PDGF-BB, RANTES, TNF-α, and VEGF was evaluated in the plasma of 19 healthy individuals. We studied rela- tionship between mRNA levels of chemokines/recaptors and cytokine concentration in blood of healthy volunteers. Conclusion: These data are allowed to assess chemokines impact in the cytokine regulation of healthy subjects. These results indicate that chemokines and their receptors is diverse and redundant system of immune reactivity in response to internal and external challenges.

Keywords

Chemokines; Chemokine Receptors; mRNA; Cytokines; Healthy Volunteers

Conflicts of Interest

The authors declare no conflicts of interest.

References

[1]	Hu, Z. (2009) Insight into microRNA regulation by analyzing the characteristics of their targets in humans. BMC Genomics, 10, 594. http://www.biomedcentral.com/content/pdf/1471-2164-10-594.pdf doi:10.1186/1471-2164-10-594
[2]	Perry, M.M., Moschos, S.A., Williams, A.E., Shepherd, N.J., Larner-Svensson, H.M. and Lindsay, M.A. (2008) Rapid changes in microRNA-146a expression negatively regulate the IL-1β-induced inflammatory response in human lung alveolar epithelial cells. Journal of Immunology, 180, 5689-5698.
[3]	Pope, S.M., Fulkerson, P.C., Blanchard, C., Akei, H.S., Nikolaidis, N.M., Zimmermann, N., Molkentin, J.D. and Rothenberg, M.E. (2005) Identification of a cooperative mechanism involving interleukin-13 and eotaxin-2 in experimental allergic lung inflammation. Journal of Biological Chemistry, 280, 13952-13961. doi:10.1074/jbc.M406037200
[4]	Scheicher, M.E., Teixeira, M.M., Cunha, F.Q., Teixeira Jr., A.L., Filho, J.T. and Vianna E.O. (2007) Eotaxin-2 in sputum cell culture to evaluate asthma inflammation. European Respiratory Journal, 29, 3489-3495. doi:10.1183/09031936.00060205
[5]	Ochkur, S.I., Jacobsen, E.A., Protheroe, C.A., Biechele, T.L., Pero, R.S., McGarry, M.P., Wang, H., O’Neill, K.R., Colbert, D.C., Colby, T.V., Shen, H., Blackburn, M.R., Irvin, C.C., Lee, J.J. and Lee, N.A. (2007) Coexpression of IL-5 and eotaxin-2 in mice creates an eosinophil-dependent model of respiratory inflammation with characteristics of severe asthma. Journal of Immunology, 178, 7879-7889.
[6]	Haley, K.J., Sunday, M.E., Porrata, Y., Kelley, C., Twomey, A., Shahsafaei, A., Galper, B., Sonna, L.A. and Lilly, C.M. (2008) Ontogeny of the eotaxins in human lung. American Journal of Physiology—Lung Cellular and Molecular Physiology, 294, L214-L224. doi:10.1152/ajplung.00086.2007
[7]	Beck, L.A., Tancowny, B., Brummet, M.E., Asaki, S.Y., Curry, S.L., Penno, M.B., Foster, M., Bahl, A. and Stellato, C. (2006) Functional analysis of the chemokine receptor CCR3 on airway epithelial cells. Journal of Immunology, 177, 3344-3354.
[8]	Nigo, Y.I., Yamashita, M., Hirahara, K., Shinnakasu, R., Inami, M., Kimura, M., Hasegawa, A., Kohno, Y. and Nakayama, T. (2006) Regulation of allergic airway inflammation through Toll-like receptor 4-mediated modification of mast cell function. Proceedings of the National Academy of Sciences of the United States of America, 103, 2286-2291. doi:10.1073/pnas.0510685103
[9]	Rehani, K., Wang, H., Garcia, C.A., Kinane, D.F. and Martin, M. (2009) Toll-like receptor-mediated production of IL-1Ra is negatively regulated by GSK3 via the MAPK ERK1/2. Journal of Immunology, 182, 547-553.
[10]	Pope, S.M., Zimmermann, N., Stringer, K.F., Karow, M.L., Rothenberg, M.E. (2005) The eotaxin chemokines and CCR3 are fundamental regulators of allergen-induced pulmonary eosinophilia. Journal of Immunology, 175, 53415350.
[11]	Ogilvie, P., Thelen, S., Moepps, B., Gierschik, P., da Silva Campos, A.C., Baggiolini, M. and Thelen, M. (2004) Unusual chemokine receptor antagonism involving a mitogen-activated protein kinase pathway. Journal of Immunology, 172, 6715-6722.
[12]	Wong, C.K., Cheung, P.F.Y., Ip, W.K. and Lam, C.W.K. (2007) Intracellular signaling mechanisms regulating Toll-like receptor-mediated activation of eosinophils. American Journal of Respiratory Cell and Molecular Biology, 37, 85-96. doi:10.1165/rcmb.2006-0457OC
[13]	Zhang, Q.-P., Xie, L.-K., Zhang, L.-J. and Tan, J.-Q. (2005) Apoptosis in human germinal centre B cells by means of CC chemokine receptor 3 expression induced by interleukin-2 and interleukin-4. Chinese Medical Journal, 118, 665-670.
[14]	Yoshida, N., Aizu-Yokota, E., Sonoda, Y., Moriwaki, Y., Kishi, K. and Kasahara, T. (2007) Production and regulation of eotaxin-2/CCL24 in a differentiated human leukemic cell line, HT93. Biological Pharmaceutical Bulletin, 30, 1826-1832. doi:10.1248/bpb.30.1826
[15]	Kelly, E.A.B., Koziol-White, C.J., Clay, K.J., Lin, Y.L., Bates, M.E., Bertics, P.J. and Jarjour, N.N. (2009) Potential contribution of IL-7 to allergen-induced eosinophilic airway inflammation in asthma. Journal of Immunology, 182, 1404-1410.
[16]	Shimbara, A., Christodoulopoulos, P., Soussi-Gounni, A., Olivenstein, R., Nakamura, Y., Levitt, R., Nicolaides, N., Holroyd, K., Tsicopoulos, A., Lafitte, J., Wallaert, B. and Hamid, Q.A. (2000) IL-9 and its receptor in allergic and nonallergic lung disease: Increased expression in asthma. Journal of Allergy and Clinical Immunology, 105, 108115. doi:10.1016/S0091-6749(00)90185-4
[17]	Cheung, P.F.Y., Wong, C.K. and Lam, C.W.K. (2008) Molecular mechanisms of cytokine and chemokine release from eosinophils activated by IL-17A, IL-17F, and IL-23: Implication for Th17 lymphocytes-mediated allergic inflammation. Journal of Immunology, 180, 56255635.
[18]	Rahman, M.S., Yamasaki, A., Yang, J., Shan, L., Halayko, A.J. and Gounni, A.S. (2006) IL-17A induces eotaxin-1/CC chemokine ligand 11 expression in human airway smooth muscle cells: role of MAPK (Erk1/2, JNK, and p38) pathways. Journal of Immunology, 177, 40644071.
[19]	Spencer, L.A., Szela, C.T., Perez, S.A.C., Kirchhoffer, C.L., Neves, J.S., Radke, A.L. and Weller, P.F. (2009) Human eosinophils constitutively express multiple Th1, Th2, and immunoregulatory cytokines that are secreted rapidly and differentially. Journal of Leukocyte Biology, 85, 117-123. doi:10.1189/jlb.0108058
[20]	Allan, S.E., Crome, S.Q., Crellin, N.K., Passerini, L., Steiner, T.S., Bacchetta, R., Roncarolo, M.G. and Levings, M.K. (2007) Activation-induced FOXP3 in human T effector cells does not suppress proliferation or cytokine production. International Immunology, 19, 345-354. doi:10.1093/intimm/dxm014
[21]	McCarron, M. and Reen, D.J. (2009) Activated human neonatal CD8+ T cells are subject to immunomodulation by direct TLR2 or TLR5 stimulation. Journal of Immunology, 182, 55-62.
[22]	Mueller, T., Terada, T., Rosenberg, I.M., Shibolet, O. and Podolsky, D.K. (2006) Th2 cytokines down-regulate TLR expression and function in human intestinal epithelial cells. Journal of Immunology, 176, 5805-5814.
[23]	M?nsson, A. and Cardell, L.-O. (2009) Role of atopic status in Toll-like receptor (TLR)7and TLR9-mediated activation of human eosinophils. Journal of Leukocyte Biology, 85, 719-727. doi:10.1189/jlb.0808494
[24]	Tomanek, R.J., Hansen, H.K. and Christensen, L.P. (2008) Temporally expressed PDGF and FGF-2 regulate embryonic coronary artery formation and growth. Arteriosclerosis, Thrombosis, and Vascular Biology, 28, 12371243. doi:10.1161/ATVBAHA.108.166454
[25]	Faraone, D., Aguzzi, M.S., Ragone, G., Russo, K., Capogrossi, M.C. and Facchiano, A. (2006) Heterodimerization of FGF-receptor 1 and PDGF-receptor-α: A novel mechanism underlying the inhibitory effect of PDGF-BB on FGF-2 in human cells. Blood, 107, 1896-1902. doi:10.1182/blood-2005-04-1524
[26]	Petreaca, M.L., Yao, M., Liu, Y., DeFea, K. and Martins-Green, M. (2007) Transactivation of vascular endothelial growth factor receptor-2 by interleukin-8 (IL-8/ CXCL8) is required for IL-8/CXCL8-induced endothelial permeability. Molecular Biology of the Cell, 18, 50145023. doi:10.1091/mbc.E07-01-0004
[27]	Ramos, C.D.L., Canetti, C., Souto, J.T., Silva, J.S., Hogaboam, C.M., Ferreira, S.H. and Cunha, F.Q. (2005) MIP-1α (CCL3) acting on the CCR1 receptor mediates neutrophil migration in immune inflammation via sequential release of TNF-α and LTB4. Journal of Leukocyte Biology, 78, 167-177. doi:10.1189/jlb.0404237
[28]	Herd, K.A., Nelson, M., Mahalingam, S. and Tindle, R.W.J. (2010) Pulmonary infection of mice with human metapneumovirus induces local cytotoxic T-cell and immunoregulatory cytokine responses similar to those seen with human respiratory syncytial virus. Journal of General Virology, 91, 1302-1310. doi:10.1099/vir.0.015396-0
[29]	Lerner, C.G., Horton, M.R., Schwartz, R.H. and Powell, J.D. (2000) Distinct requirements for C-C chemokine and IL-2 production by naive, previously activated, and anergic T cells. Journal of Immunology, 164, 3996-4002