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Published in: Inflammation 6/2015

01-12-2015

P2X7 Receptor Expression in Peripheral Blood Monocytes Is Correlated With Plasma C-Reactive Protein and Cytokine Levels in Patients With Type 2 Diabetes Mellitus: a Preliminary Report

Authors: Hong Wu, Yijun Nie, Huangui Xiong, Shuangmei Liu, Guilin Li, An Huang, Lili Guo, Shouyu Wang, Yun Xue, Bing Wu, Lichao Peng, Miaomiao Song, Guodong Li, Shangdong Liang

Published in: Inflammation | Issue 6/2015

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Abstract

Chronic inflammation plays a major role in development of type 2 diabetes mellitus (T2DM). C-reactive protein (CRP) and inflammatory cytokines such as tumor necrosis factor-α (TNF-α) and interleukin 1β (IL-1β) are directly involved in the occurrence of insulin resistance. Increased extracellular ATP levels can amplify the inflammatory response in vivo via the P2X7 receptor. The present study aimed to assess the relationship between P2X7 receptor expression in human peripheral blood monocytes and plasma levels of TNF-α, IL-1β, and CRP in T2DM patients. The results showed the association of increased P2X7 receptor expression of monocytes with high serum CRP, TNF-α, and IL-1β levels. TNF-α and IL-1β levels were lowest in healthy subjects; in T2DM patients, these inflammatory markers were less abundant in individuals with normal CRP levels compared to those with high CRP contents. In contrast, IL-10 levels in T2DM patients with high CRP levels were dramatically decreased. P2X7 receptor expression in monocytes from T2DM patients with high CRP levels was significantly increased in comparison with healthy individuals and T2DM patients with normal CRP levels. These findings indicated that P2X7 receptor in peripheral blood monocytes may be involved in the pathological changes of T2DM, particularly affecting patients with high CRP levels.
Literature
1.
go back to reference Esser, N., S. Legrand-Poels, J. Piette, A.J. Scheen, and N. Paquot. 2014. Inflammation as a link between obesity, metabolic syndrome and type 2 diabetes. Diabetes Research and Clinical Practice 1054: 141–150.CrossRef Esser, N., S. Legrand-Poels, J. Piette, A.J. Scheen, and N. Paquot. 2014. Inflammation as a link between obesity, metabolic syndrome and type 2 diabetes. Diabetes Research and Clinical Practice 1054: 141–150.CrossRef
2.
go back to reference Fernández-Real, J.M., and J.C. Pickup. 2012. Innate immunity, insulin resistance and type 2 diabetes. Diabetologia 55: 273–278.CrossRefPubMed Fernández-Real, J.M., and J.C. Pickup. 2012. Innate immunity, insulin resistance and type 2 diabetes. Diabetologia 55: 273–278.CrossRefPubMed
3.
go back to reference Wellen, K.E., and G.S. Hotamisligil. 2005. Inflammation, stress, and diabetes. Journal of Clinical Investigation 1155: 1111–1119.CrossRef Wellen, K.E., and G.S. Hotamisligil. 2005. Inflammation, stress, and diabetes. Journal of Clinical Investigation 1155: 1111–1119.CrossRef
4.
go back to reference Mirza, S., M. Hossain, C. Mathews, P. Martinez, P. Pino, J.L. Gay, A. Rentfro, J.B. McCormick, and S.P. Fisher-Hoch. 2012. Type 2 diabetes is associated with elevated levels of TNF-alpha, IL-6 and adiponectin and low levels of leptin in a population of Mexican Americans: a cross-sectional study. Cytokine 57: 136–142.PubMedCentralCrossRefPubMed Mirza, S., M. Hossain, C. Mathews, P. Martinez, P. Pino, J.L. Gay, A. Rentfro, J.B. McCormick, and S.P. Fisher-Hoch. 2012. Type 2 diabetes is associated with elevated levels of TNF-alpha, IL-6 and adiponectin and low levels of leptin in a population of Mexican Americans: a cross-sectional study. Cytokine 57: 136–142.PubMedCentralCrossRefPubMed
5.
go back to reference Saraswathi, V., C.J. Ramnanan, A.W. Wilks, C.V. Desouza, A.A. Eller, G. Murali, R. Ramalingam, G.L. Milne, K.C. Coate, and D.S. Edgerton. 2013. Impact of hematopoietic cyclooxygenase-1 deficiency on obesity-linked adipose tissue inflammation and metabolic disorders in mice. Metabolism: clinical and experimental 6211: 1673–1685.CrossRef Saraswathi, V., C.J. Ramnanan, A.W. Wilks, C.V. Desouza, A.A. Eller, G. Murali, R. Ramalingam, G.L. Milne, K.C. Coate, and D.S. Edgerton. 2013. Impact of hematopoietic cyclooxygenase-1 deficiency on obesity-linked adipose tissue inflammation and metabolic disorders in mice. Metabolism: clinical and experimental 6211: 1673–1685.CrossRef
6.
go back to reference Wang, Z.Q., and W.E. Hoy. 2007. C-reactive protein and the risk of developing type 2 diabetes in Aboriginal Australians. Diabetes Research and Clinical Practice 7612: 37–43.CrossRef Wang, Z.Q., and W.E. Hoy. 2007. C-reactive protein and the risk of developing type 2 diabetes in Aboriginal Australians. Diabetes Research and Clinical Practice 7612: 37–43.CrossRef
7.
go back to reference Pradhan, R., D. Fong, C. March, R. Jack, G. Rezapour, K. Norris, and M.B. Davidson. 2002. Angiotensin-converting enzyme inhibition for the treatment of moderate to severe diabetic retinopathy in normotensive type 2 diabetic patients: a pilot study. Journal of Diabetes and Its Complications 165: 377–381.CrossRef Pradhan, R., D. Fong, C. March, R. Jack, G. Rezapour, K. Norris, and M.B. Davidson. 2002. Angiotensin-converting enzyme inhibition for the treatment of moderate to severe diabetic retinopathy in normotensive type 2 diabetic patients: a pilot study. Journal of Diabetes and Its Complications 165: 377–381.CrossRef
8.
go back to reference Wiley, J.S., and B.J. Gu. 2012. A new role for the P2X7 receptor: a scavenger receptor for bacteria and apoptotic cells in the absence of serum and extracellular ATP. Purinergic Signalling 83: 579–586.CrossRef Wiley, J.S., and B.J. Gu. 2012. A new role for the P2X7 receptor: a scavenger receptor for bacteria and apoptotic cells in the absence of serum and extracellular ATP. Purinergic Signalling 83: 579–586.CrossRef
9.
go back to reference Zhang, X.J., G.G. Zheng, X.T. Ma, Y.M. Lin, Y.H. Song, and K.F. Wu. 2005. Effects of various inducers on the expression of P2X7 receptor in human peripheral blood mononuclear cells. Shengli Xuebao 572: 193–198. Zhang, X.J., G.G. Zheng, X.T. Ma, Y.M. Lin, Y.H. Song, and K.F. Wu. 2005. Effects of various inducers on the expression of P2X7 receptor in human peripheral blood mononuclear cells. Shengli Xuebao 572: 193–198.
10.
go back to reference Lister, M.F., J. Sharkey, D.A. Sawatzky, J.P. Hodgkiss, D.J. Davidson, A.G. Rossi, and K. Finlayson. 2007. The role of the purinergic P2X7 receptor in inflammation. Journal of Inflammation 4: 5.PubMedCentralCrossRefPubMed Lister, M.F., J. Sharkey, D.A. Sawatzky, J.P. Hodgkiss, D.J. Davidson, A.G. Rossi, and K. Finlayson. 2007. The role of the purinergic P2X7 receptor in inflammation. Journal of Inflammation 4: 5.PubMedCentralCrossRefPubMed
11.
go back to reference Masin, M., C. Young, K. Lim, S.J. Barnes, X.J. Xu, V. Marschall, W. Brutkowski, E.R. Mooney, D.C. Gorecki, and R. Murrell-Lagnado. 2012. Expression, assembly and function of novel C-terminal truncated variants of the mouse P2X7 receptor: re-evaluation of P2X7 knockouts. British Journal of Pharmacology 1654: 135–143. Masin, M., C. Young, K. Lim, S.J. Barnes, X.J. Xu, V. Marschall, W. Brutkowski, E.R. Mooney, D.C. Gorecki, and R. Murrell-Lagnado. 2012. Expression, assembly and function of novel C-terminal truncated variants of the mouse P2X7 receptor: re-evaluation of P2X7 knockouts. British Journal of Pharmacology 1654: 135–143.
12.
go back to reference Mehta, N., M. Kaur, M. Singh, S. Chand, B. Vyas, P. Silakari, M.S. Bahia, and O. Silakari. 2014. Purinergic receptor P2X7: a novel target for anti-inflammatory therapy. Bioorganic & Medicinal Chemistry 22: 54–88.CrossRef Mehta, N., M. Kaur, M. Singh, S. Chand, B. Vyas, P. Silakari, M.S. Bahia, and O. Silakari. 2014. Purinergic receptor P2X7: a novel target for anti-inflammatory therapy. Bioorganic & Medicinal Chemistry 22: 54–88.CrossRef
14.
go back to reference Marques da Silva, C., L.M. Rodrigues, A. Passos da Silva Gomes, M. Mantuano Barradas, F. Sarmento Vieira, P.M. Persechini, and R. Coutinho-Silva. 2008. Modulation of P2X7 receptor expression in macrophages from mineral oil-injected mice. Immunobiology 213: 481–492.CrossRefPubMed Marques da Silva, C., L.M. Rodrigues, A. Passos da Silva Gomes, M. Mantuano Barradas, F. Sarmento Vieira, P.M. Persechini, and R. Coutinho-Silva. 2008. Modulation of P2X7 receptor expression in macrophages from mineral oil-injected mice. Immunobiology 213: 481–492.CrossRefPubMed
15.
go back to reference Calabro, P., D.W. Chang, J.T. Willerson, and E.T.H. Yeh. 2005. Release of C-reactive protein in response to inflammatory cytokines by human adipocytes: linking obesity to vascular inflammation. Journal of the American College of Cardiology 46: 1112–1113.CrossRefPubMed Calabro, P., D.W. Chang, J.T. Willerson, and E.T.H. Yeh. 2005. Release of C-reactive protein in response to inflammatory cytokines by human adipocytes: linking obesity to vascular inflammation. Journal of the American College of Cardiology 46: 1112–1113.CrossRefPubMed
16.
go back to reference Priori, R., C. Alessandri, L. Magrini, E.A.M. Cassarà, F. Ceccarelli, M. Modesti, C. Croia, M. Bombardieri, and G. Valesini. 2009. Nucleosome accumulation and reduction of C-reactive protein are associated with the generation of anti-nuclear antibodies in patients with rheumatoid arthritis treated with adalimumab, but not with etanercept. ARD Online 68: 1514–1516. Priori, R., C. Alessandri, L. Magrini, E.A.M. Cassarà, F. Ceccarelli, M. Modesti, C. Croia, M. Bombardieri, and G. Valesini. 2009. Nucleosome accumulation and reduction of C-reactive protein are associated with the generation of anti-nuclear antibodies in patients with rheumatoid arthritis treated with adalimumab, but not with etanercept. ARD Online 68: 1514–1516.
17.
go back to reference Doi, Y., Y. Kiyohara, M. Kubo, T. Ninomiya, Y. Wakugawa, K. Yonemoto, M. Iwase, and M. Iida. 2005. Elevated C-reactive protein is a predictor of the development of diabetes in a general Japanese population: the Hisayama Study. Diabetes Care 28: 2497–2500.CrossRefPubMed Doi, Y., Y. Kiyohara, M. Kubo, T. Ninomiya, Y. Wakugawa, K. Yonemoto, M. Iwase, and M. Iida. 2005. Elevated C-reactive protein is a predictor of the development of diabetes in a general Japanese population: the Hisayama Study. Diabetes Care 28: 2497–2500.CrossRefPubMed
18.
19.
go back to reference Abbas, D., K. Isabella, M. de Maat, P.M. Uitterlinden, G. Andre, E. Sijbrands, J.G. Bootsma, H. Aart, T. Stijnen, A. Hofman, M. Schram, T. Witteman, and C.M. Jacqueline. 2007. Genetic variation, C-reactive protein levels, and incidence of diabetes. Diabetes 56(3): 872–878.CrossRef Abbas, D., K. Isabella, M. de Maat, P.M. Uitterlinden, G. Andre, E. Sijbrands, J.G. Bootsma, H. Aart, T. Stijnen, A. Hofman, M. Schram, T. Witteman, and C.M. Jacqueline. 2007. Genetic variation, C-reactive protein levels, and incidence of diabetes. Diabetes 56(3): 872–878.CrossRef
20.
go back to reference Zieleniak, A., K. Cypryk, L.A. Wozniak, M. Bieńkiewicz, and M. Wójcik. 2012. Adenosine receptors expression is elevated in leukocytes of gestational diabetes mellitus (GDM) subjects—a preliminary study. Endokrynologia Polska 63: 110–114.PubMed Zieleniak, A., K. Cypryk, L.A. Wozniak, M. Bieńkiewicz, and M. Wójcik. 2012. Adenosine receptors expression is elevated in leukocytes of gestational diabetes mellitus (GDM) subjects—a preliminary study. Endokrynologia Polska 63: 110–114.PubMed
21.
go back to reference Glas, R., N.S. Sauter, F.T. Schulthess, L. Shu, J. Oberholzer, and K. Maedler. 2009. Purinergic P2X7 receptors regulate secretion of interleukin-1 receptor antagonist and beta cell function and survival. Diabetologia 52: 1579–1588.PubMedCentralCrossRefPubMed Glas, R., N.S. Sauter, F.T. Schulthess, L. Shu, J. Oberholzer, and K. Maedler. 2009. Purinergic P2X7 receptors regulate secretion of interleukin-1 receptor antagonist and beta cell function and survival. Diabetologia 52: 1579–1588.PubMedCentralCrossRefPubMed
22.
go back to reference García-Hernández, M.H., L. Portales-Cervantes, N. Cortez-Espinosa, J.M. Vargas-Morales, J.F.F. Salazar, E. Rivera-López, J.G. Rodríguez-Rivera, R. Quezada-Calvillo, and D.P. Portales-Pérez. 2011. Expression and function of P2X7 receptor and CD39/Entpd1 in patients with type 2 diabetes and their association with biochemical parameters. Cellular Immunology 269: 135–143.CrossRefPubMed García-Hernández, M.H., L. Portales-Cervantes, N. Cortez-Espinosa, J.M. Vargas-Morales, J.F.F. Salazar, E. Rivera-López, J.G. Rodríguez-Rivera, R. Quezada-Calvillo, and D.P. Portales-Pérez. 2011. Expression and function of P2X7 receptor and CD39/Entpd1 in patients with type 2 diabetes and their association with biochemical parameters. Cellular Immunology 269: 135–143.CrossRefPubMed
24.
go back to reference Rhee, E.J., Y.C. Kim, W.Y. Lee, C.H. Jung, K.C. Sung, S.H. Ryu, K.W. Oh, and S.W. Kim. 2006. Comparison of insulin resistance and serum high-sensitivity C-reactive protein levels according to the fasting blood glucose subgroups divided by the newly recommended criteria for fasting hyperglycemia in 10059 healthy Koreans. Metabolism 55: 183–187.CrossRefPubMed Rhee, E.J., Y.C. Kim, W.Y. Lee, C.H. Jung, K.C. Sung, S.H. Ryu, K.W. Oh, and S.W. Kim. 2006. Comparison of insulin resistance and serum high-sensitivity C-reactive protein levels according to the fasting blood glucose subgroups divided by the newly recommended criteria for fasting hyperglycemia in 10059 healthy Koreans. Metabolism 55: 183–187.CrossRefPubMed
25.
go back to reference Elawa, G., A.M. AoudAllah, A.E. Hasaneen, and A.M. El-Hammady. 2011. The predictive value of serum mannan-binding lectin levels for diabetic control and renal complications in type2 diabetic patients. Saudi Medical Journal 32: 784–790.PubMed Elawa, G., A.M. AoudAllah, A.E. Hasaneen, and A.M. El-Hammady. 2011. The predictive value of serum mannan-binding lectin levels for diabetic control and renal complications in type2 diabetic patients. Saudi Medical Journal 32: 784–790.PubMed
26.
go back to reference Medzhitov, R., and C.A. Janeway Jr. 2000. How does the immune system distinguish self from non-self? Immunology 12: 185–188. Medzhitov, R., and C.A. Janeway Jr. 2000. How does the immune system distinguish self from non-self? Immunology 12: 185–188.
27.
go back to reference Generaal, E., N. Vogelzangs, G.J. Macfarlane, R. Geenen, J.H. Smit, J. Dekker, and B.W.J.H. Penninx. 2014. Basal inflammation and innate immune response in chronic multisite musculoskeletal pain. Pain 155: 1605–1612.CrossRefPubMed Generaal, E., N. Vogelzangs, G.J. Macfarlane, R. Geenen, J.H. Smit, J. Dekker, and B.W.J.H. Penninx. 2014. Basal inflammation and innate immune response in chronic multisite musculoskeletal pain. Pain 155: 1605–1612.CrossRefPubMed
Metadata
Title
P2X7 Receptor Expression in Peripheral Blood Monocytes Is Correlated With Plasma C-Reactive Protein and Cytokine Levels in Patients With Type 2 Diabetes Mellitus: a Preliminary Report
Authors
Hong Wu
Yijun Nie
Huangui Xiong
Shuangmei Liu
Guilin Li
An Huang
Lili Guo
Shouyu Wang
Yun Xue
Bing Wu
Lichao Peng
Miaomiao Song
Guodong Li
Shangdong Liang
Publication date
01-12-2015
Publisher
Springer US
Published in
Inflammation / Issue 6/2015
Print ISSN: 0360-3997
Electronic ISSN: 1573-2576
DOI
https://doi.org/10.1007/s10753-015-0189-y

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