1. P. P. Lie, C. Y. Cheng and D. D. Mruk (2011) Interleukin-1alpha is a regulator of the blood-testis barrier. FASEB J 25(4): 1244-53.
Abstract Throughout spermatogenesis, the Sertoli cell blood-testis barrier (BTB) is strictly regulated by cytokines, which mediate its timely restructuring, thereby allowing spermatocytes to enter the adluminal compartment of the seminiferous epithelium for development into spermatozoa. The aim herein was to investigate whether germ cells play a role in BTB restructuring via the action of interleukin-1alpha (IL-1alpha) since germ cells are known to control Sertoli cell production of this cytokine, and if yes, how these effects are mediated. When Sertoli cells were isolated from Sprague-Dawley rats and plated at high density, IL-1alpha (100 pg/ml) was shown to "open" the Sertoli cell barrier when its integrity was assessed by transepithelial electrical resistance measurements. Further investigation of Sertoli cells treated with IL-1alpha revealed striking changes in the cellular distribution of actin filaments when compared to untreated cells. These effects at the Sertoli cell barrier were mediated, in part, by epidermal growth factor receptor pathway substrate 8 (Eps8; an actin bundling and barbed-end capping protein) and actin-related protein 3 (Arp3; a component of the actin nucleation machinery). As important, an increase in the kinetics of occludin internalization but a decrease in its rate of degradation was noted following IL-1alpha treatment. These results indicate that IL-1alpha is a critical regulator of BTB dynamics. PMID: [21191089]
2. O. Sarkar, P. P. Mathur, C. Y. Cheng and D. D. Mruk (2008) Interleukin 1 alpha (IL1A) is a novel regulator of the blood-testis barrier in the rat. Biol Reprod 78(3): 445-54.
Abstract Throughout spermatogenesis, leptotene spermatocytes must traverse the blood-testis barrier (BTB) at stages VIII-XI to gain entry into the adluminal compartment for continued development. However, the mechanism underlying BTB restructuring remains somewhat elusive. In this study, interleukin 1 alpha (IL1A) was administered intratesticularly to adult rats in order to assess its effects on spermatogenesis. IL1A was shown to perturb Sertoli-germ cell adhesion, resulting in germ cell loss from approximately 50% of seminiferous tubules by 15 days posttreatment. Equally important, the functional integrity of the BTB was compromised when inulin-fluorescein isothiocyanate was detected in the adluminal compartment of the seminiferous epithelium following its administration via the jugular vein. Interestingly, IL1A did not affect the steady-state levels of proteins that confer BTB function, namely OCLN, CLDN1, F11R, TJP1, and CDH2. Instead, the localizations of OCLN, F11R, and TJP1 in the seminiferous epithelium were altered; these proteins appeared to move away from sites of cell-cell contact. Moreover, IL1A was shown to perturb the orderly arrangement of filamentous actin at the BTB and apical ectoplasmic specialization with distinct areas illustrating loss of actin filaments. Taken collectively, these results suggest that IL1A-induced BTB disruption is not mediated via the reduction of target protein levels. Instead, IL1A's primary cellular target appears to be the Sertoli cell actin cytoskeleton. It is possible that localized production of IL1A by Sertoli and/or germ cells in vivo results in BTB restructuring, and this may facilitate the movement of leptotene spermatocytes across the BTB. PMID: [18057314]
3. C. K. Jonsson, R. H. Zetterstrom, M. Holst, M. Parvinen and O. Soder (1999) Constitutive expression of interleukin-1alpha messenger ribonucleic acid in rat Sertoli cells is dependent upon interaction with germ cells. Endocrinology 140(8): 3755-61.
Abstract Interleukin-1 (IL-1), a proinflammatory cytokine originally isolated as a product of activated mononuclear phagocytes, consists of two distinct agonist proteins, IL-1alpha and IL-1beta, of which IL-1beta is the major inducible IL-1 protein produced by macrophages. We show here that mRNA of IL-1alpha, but not IL-1beta, is constitutively expressed by the intact rat testis and localize the transcript to Sertoli cells as confirmed by a novel squash technique. The expression is developmentally regulated and appears only after postnatal day 20 in the rat testis, corresponding to onset of puberty. IL-1alpha mRNA shows a stage-dependent expression pattern during the cycle of the seminiferous epithelium. It is low or absent in stage VII, but present in all other stages of the cycle. The same stage-dependent distribution was also observed at the protein level when bioactive IL-1 was measured in extracts of accurately defined one millimeter segments of seminiferous tubules. No IL-1alpha mRNA was detected in adult rat testes after germ cell depletion by fetal irradiation or cytostatic drug treatment. Because stage VII is the only segment of the seminiferous tubules lacking DNA replication, we propose that IL-1alpha is involved in this event during mitosis and meiosis of spermatogenesis and that its expression is dependent upon interactions between Sertoli cells and germ cells. PMID: [10433236]
Figures for illustrating the function of this protein/gene
Ref: O. Sarkar, P. P. Mathur, C. Y. Cheng and D. D. Mruk (2008) Interleukin 1 alpha (IL1A) is a novel regulator of the blood-testis barrier in the rat. Biol Reprod 78(3): 445-54. PMID: [18057314]
Ref: O. Sarkar, P. P. Mathur, C. Y. Cheng and D. D. Mruk (2008) Interleukin 1 alpha (IL1A) is a novel regulator of the blood-testis barrier in the rat. Biol Reprod 78(3): 445-54. PMID: [18057314]
Ref: O. Sarkar, P. P. Mathur, C. Y. Cheng and D. D. Mruk (2008) Interleukin 1 alpha (IL1A) is a novel regulator of the blood-testis barrier in the rat. Biol Reprod 78(3): 445-54. PMID: [18057314]
Ref: O. Sarkar, P. P. Mathur, C. Y. Cheng and D. D. Mruk (2008) Interleukin 1 alpha (IL1A) is a novel regulator of the blood-testis barrier in the rat. Biol Reprod 78(3): 445-54. PMID: [18057314]
Ref: O. Sarkar, P. P. Mathur, C. Y. Cheng and D. D. Mruk (2008) Interleukin 1 alpha (IL1A) is a novel regulator of the blood-testis barrier in the rat. Biol Reprod 78(3): 445-54. PMID: [18057314]
Ref: C. K. Jonsson, R. H. Zetterstrom, M. Holst, M. Parvinen and O. Soder (1999) Constitutive expression of interleukin-1alpha messenger ribonucleic acid in rat Sertoli cells is dependent upon interaction with germ cells. Endocrinology 140(8): 3755-61. PMID: [10433236]
Ref: C. K. Jonsson, R. H. Zetterstrom, M. Holst, M. Parvinen and O. Soder (1999) Constitutive expression of interleukin-1alpha messenger ribonucleic acid in rat Sertoli cells is dependent upon interaction with germ cells. Endocrinology 140(8): 3755-61. PMID: [10433236]
Ref: C. K. Jonsson, R. H. Zetterstrom, M. Holst, M. Parvinen and O. Soder (1999) Constitutive expression of interleukin-1alpha messenger ribonucleic acid in rat Sertoli cells is dependent upon interaction with germ cells. Endocrinology 140(8): 3755-61. PMID: [10433236]
Ref: C. K. Jonsson, R. H. Zetterstrom, M. Holst, M. Parvinen and O. Soder (1999) Constitutive expression of interleukin-1alpha messenger ribonucleic acid in rat Sertoli cells is dependent upon interaction with germ cells. Endocrinology 140(8): 3755-61. PMID: [10433236]
Function
Produced by activated macrophages, IL-1 stimulatesthymocyte proliferation by inducing IL-2 release, B-cellmaturation and proliferation, and fibroblast growth factoractivity. IL-1 proteins are involved in the inflammatory response,being identified as endogenous pyrogens, and are reported tostimulate the release of prostaglandin and collagenase fromsynovial cells (By similarity).