Aim: The expression of the cytokines IL-2, IL-6, IL-10, IFN-γ and TNF-α and the adhesion proteins CD99 and CD106 was studied in the human testis at the protein level. Methods: The expression of the cytokines and the...Aim: The expression of the cytokines IL-2, IL-6, IL-10, IFN-γ and TNF-α and the adhesion proteins CD99 and CD106 was studied in the human testis at the protein level. Methods: The expression of the cytokines and the adhesion proteins was assessed using immunohistochemistry and immunoblotting. Results: None of the cytokines studied was present in the human testis, but CD99 and CD106 (VCAM-1) strongly were expressed in all the testes investigated. CD99 was present in the interstitial tissue of the human testis as well as in the Sertoli cells. The identity of the CD99+ interstitial cells is unclear. CD106 (VCAM-1) was present in Leydig cells as well as the basal parts of the Sertoli cells in the seminiferous tubules. In immunoblotting, CD99 was demonstrated at molecular ratios of 46-57 (kD). This is a novel isoform of the molecule. Conclusion: The human testis produces both CD99 and CD106 and as CD106 mediates cell binding to lymphocytes, it is possible that the human Leydig cells adhere to lymphocytes like the rodent Leydig cells. (Asian J Androl 2002 Dec; 4: 243-248)展开更多
Exposure to pathogens induces antigen-presenting cells （APC） such as macrophages and dendritic cells （DC） to produce various endogenous mediators, including arachidonic acid （AA）-derived eicosanoids, cytokines, ...Exposure to pathogens induces antigen-presenting cells （APC） such as macrophages and dendritic cells （DC） to produce various endogenous mediators, including arachidonic acid （AA）-derived eicosanoids, cytokines, and nitric oxide （NO）. Many secreted products of activated APC can act by themselves in an autocrine manner and modulate their function. Moreover, the cross-interaction between endogenous bioactive molecules regulates the function of professional APC with important consequences for their ability to activate and sustain immune and inflammatory responses, and to regulate immune homeostasis. Although neglected for many years when compared to their role in cardiovascular homeostasis, cancer and inflammation, the importance of eicosanoids in immunology is becoming more defined. The role of prostaglandin （PG） E2 （PGE2）, one of the best known and most well studied eicosanoids, is of particular interest. It modulates the activities of professional DC by acting on their differentiation, maturation and their ability to secrete cytokines. Uniquely among haematopoietic cytokines, interleukin-10 （IL-10） is a pleiotropic molecule that displays both immunostimulatory and immunoregulatory activities. IL-10 has attached much attention because of its anti-inflammatory properties. It modulates expression of cytokines, soluble mediators and cell surface molecules by cells of myeloid origin, particularly macrophages and DC. We previously reported that PGE2 is a potent inducer of IL-10 in bone marrow-derived DC （BM-DC）, and PGE2-induced IL-10 is a key regulator of the BM-DC pro-inflammatory phenotype. BM-DC may be considered as an important model to study complex interactions between endogenous mediators, and autocrine IL-10 plays a pivotal role in the crossregulation of AA-derived lipid mediators, cytokines, and NO, with critical effects on immune and inflammatory responses.展开更多
T-cell-stimulating cytokines have shown promise as monotherapies or in combination with other therapeutic modalities for immunotherapy of cancer.However,their efficacy is limited due to their short half-life,pleiotrop...T-cell-stimulating cytokines have shown promise as monotherapies or in combination with other therapeutic modalities for immunotherapy of cancer.However,their efficacy is limited due to their short half-life,pleiotropic roles,and induction of severe toxicity even at therapeutic doses.To overcome these major therapeutic barriers,cytokine-based products are being further developed to improve their therapeutic index.These approaches include manipulating their activity to preferentially bind to effector immune cells rather than immune-suppressive cells,prolonging their half-life in vivo and modifying them to target tumors.This review focuses on IL-2,IL-15,and IL-10,which have potent effects on immune cells that mediate effective antitumor responses.We will summarize the recent progress of these cytokines in both preclinical studies and selective clinical applications and will discuss our perspectives on the development of new strategies to potentiate cytokine-based immunotherapy.展开更多
基金Correspondence to: Dr. Esko Verijnkorva, University of Turku, Institute of Biomedicine, Department of Anatomy, Kiinamyllynkatu 10, FIN-20520 Turku, Finland.
文摘Aim: The expression of the cytokines IL-2, IL-6, IL-10, IFN-γ and TNF-α and the adhesion proteins CD99 and CD106 was studied in the human testis at the protein level. Methods: The expression of the cytokines and the adhesion proteins was assessed using immunohistochemistry and immunoblotting. Results: None of the cytokines studied was present in the human testis, but CD99 and CD106 (VCAM-1) strongly were expressed in all the testes investigated. CD99 was present in the interstitial tissue of the human testis as well as in the Sertoli cells. The identity of the CD99+ interstitial cells is unclear. CD106 (VCAM-1) was present in Leydig cells as well as the basal parts of the Sertoli cells in the seminiferous tubules. In immunoblotting, CD99 was demonstrated at molecular ratios of 46-57 (kD). This is a novel isoform of the molecule. Conclusion: The human testis produces both CD99 and CD106 and as CD106 mediates cell binding to lymphocytes, it is possible that the human Leydig cells adhere to lymphocytes like the rodent Leydig cells. (Asian J Androl 2002 Dec; 4: 243-248)
文摘Exposure to pathogens induces antigen-presenting cells （APC） such as macrophages and dendritic cells （DC） to produce various endogenous mediators, including arachidonic acid （AA）-derived eicosanoids, cytokines, and nitric oxide （NO）. Many secreted products of activated APC can act by themselves in an autocrine manner and modulate their function. Moreover, the cross-interaction between endogenous bioactive molecules regulates the function of professional APC with important consequences for their ability to activate and sustain immune and inflammatory responses, and to regulate immune homeostasis. Although neglected for many years when compared to their role in cardiovascular homeostasis, cancer and inflammation, the importance of eicosanoids in immunology is becoming more defined. The role of prostaglandin （PG） E2 （PGE2）, one of the best known and most well studied eicosanoids, is of particular interest. It modulates the activities of professional DC by acting on their differentiation, maturation and their ability to secrete cytokines. Uniquely among haematopoietic cytokines, interleukin-10 （IL-10） is a pleiotropic molecule that displays both immunostimulatory and immunoregulatory activities. IL-10 has attached much attention because of its anti-inflammatory properties. It modulates expression of cytokines, soluble mediators and cell surface molecules by cells of myeloid origin, particularly macrophages and DC. We previously reported that PGE2 is a potent inducer of IL-10 in bone marrow-derived DC （BM-DC）, and PGE2-induced IL-10 is a key regulator of the BM-DC pro-inflammatory phenotype. BM-DC may be considered as an important model to study complex interactions between endogenous mediators, and autocrine IL-10 plays a pivotal role in the crossregulation of AA-derived lipid mediators, cytokines, and NO, with critical effects on immune and inflammatory responses.
文摘T-cell-stimulating cytokines have shown promise as monotherapies or in combination with other therapeutic modalities for immunotherapy of cancer.However,their efficacy is limited due to their short half-life,pleiotropic roles,and induction of severe toxicity even at therapeutic doses.To overcome these major therapeutic barriers,cytokine-based products are being further developed to improve their therapeutic index.These approaches include manipulating their activity to preferentially bind to effector immune cells rather than immune-suppressive cells,prolonging their half-life in vivo and modifying them to target tumors.This review focuses on IL-2,IL-15,and IL-10,which have potent effects on immune cells that mediate effective antitumor responses.We will summarize the recent progress of these cytokines in both preclinical studies and selective clinical applications and will discuss our perspectives on the development of new strategies to potentiate cytokine-based immunotherapy.
