Inflammatory mediators increase surface expression of integrin ligands, adhesion to lymphocytes, and secretion of interleukin 6 in mouse Sertoli cells.

Riccioli, Anna; Filippini, Antonio; Cesaris, Paola De; Barbacci, E; Stefanini, Mario; Starace, Giuseppe; Ziparo, Elio

doi:10.1073/pnas.92.13.5808

Cited by 98 publications

(61 citation statements)

References 40 publications

(26 reference statements)

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“…A protein band corresponding to ICAM-1 was seen in lysates from Sertoli and germ cells, as well as in the testis, and these data were in agreement with RT-PCR results (Fig. 1C), as well as with previous reports from other laboratories (De Cesaris et al, 1998;Riccioli et al, 1995).…”

Section: Resultssupporting

confidence: 93%

Intercellular adhesion molecule-1 is a regulator of blood–testis barrier function

Xiao

Cheng

Mruk

2012

Journal of Cell Science

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SummaryThe mechanism underlying the movement of preleptotene/leptotene spermatocytes across the blood-testis barrier (BTB) during spermatogenesis is not well understood largely owing to the fact that the BTB, unlike most other blood-tissue barriers, is composed of several co-existing and co-functioning junction types. In the present study, we show that intercellular adhesion molecule-1 [ICAM-1, a Sertoli and germ cell adhesion protein having five immunoglobulin (Ig)-like domains, in addition to transmembrane and cytoplasmic domains] is a regulator of BTB integrity. Initial experiments showed ICAM-1 to co-immunoprecipitate and co-localize with tight junction and basal ectoplasmic specialization proteins such as occludin and N-cadherin, which contribute to BTB function. More importantly, overexpression of ICAM-1 in Sertoli cells in vitro enhanced barrier function when monitored by transepithelial electrical resistance measurements, illustrating that ICAM-1-mediated adhesion can promote BTB integrity. On the other hand, overexpression of a truncated form of ICAM-1 that consisted only of the five Ig-like domains (sICAM-1; this form of ICAM-1 is known to be secreted) elicited an opposite effect when Sertoli cell barrier function was found to be perturbed in vitro; in this case, sICAM-1 overexpression resulted in the downregulation of several BTB constituent proteins, which was probably mediated by Pyk2/p-Pyk2-Y402 and c-Src/pSrc-Y530. These findings were expanded to the in vivo level when BTB function was found to be disrupted following sICAM-1 overexpression. These data illustrate the existence of a unique mechanism in the mammalian testis where ICAM-1 can either positively or negatively regulate BTB function.

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Section: Resultssupporting

confidence: 93%

Intercellular adhesion molecule-1 is a regulator of blood–testis barrier function

Xiao

Cheng

Mruk

2012

Journal of Cell Science

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“…After stimulation with inflammatory mediators, the Sertoli cell produces IL-6 and increases ICAM-1 and VCAM-1, known to be specific binding proteins for lymphocytes (4). These data suggest the presence of both direct and paracrine mechanisms of interaction between Sertoli and immunocompetent cells, which may be involved in the regulation of immune reactions in the testis in inflammatory and/or autoimmune diseases.…”

mentioning

confidence: 74%

“…TNF-␣ is a testicular paracrine factor, known to be produced by germ cells (21), that induces transferrin release from Sertoli cells (22) and is an important proinflammatory cytokine that induces IL-6 production and ICAM-1 and VCAM-1 expression in Sertoli cells (4). The transduction mechanisms by which these biological effects are obtained in Sertoli cells have been studied extensively (23,24).…”

mentioning

confidence: 99%

TNF-α and IFN-γ Regulate Expression and Function of the Fas System in the Seminiferous Epithelium

Riccioli

Starace

D’Alessio

et al. 2000

The Journal of Immunology

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Sertoli cells have long been considered to be involved in the regulation of the immune response in the testis. More recently, the Fas system has been implicated in the maintenance of the immune privilege in the testis as well as in the regulation of germ cell apoptosis. However, the control of Fas and Fas ligand (FasL) expression in the testis remains unknown. In the present study, we demonstrate that cultured mouse Sertoli cells constitutively express a low level of membrane-bound Fas protein, but not a soluble form of Fas. Sertoli cells stimulated with TNF-α and IFN-γ markedly increase the expression of both soluble and membrane-bound Fas in a dose-dependent manner. The up-regulated membrane-bound Fas protein is functionally active because it induces a significant level of Sertoli cell death in the presence of Neuro-2a FasL+ effector cells. Interestingly, the soluble form of Fas, which is induced by the same cytokines but has an antiapoptotic effect, is also functional. In fact, conditioned media from TNF-α-stimulated Sertoli cell cultures inhibit Neuro-2a FasL+-induced cell death. Taken together, our data suggest a possible regulatory role of TNF-α and IFN-γ on Fas-mediated apoptosis in the testis through disruption of the balance between different forms of Fas.

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“…Although additional experiments are required, the role of the pH-activated chloride current in Sertoli cells may be equivalent at the plasma membrane to that of ClC-7 in intracellular compartment by being an important player in proton-linked lactate production. An alternative role may be linked to inflammation of the testis in which Sertoli cells are important players (38), and many inflammatory conditions are accompanied by local tissue acidosis with severe acidification (pH Ͻ 6).…”

Section: Discussionmentioning

confidence: 99%

A Novel Voltage-dependent Chloride Current Activated by Extracellular Acidic pH in Cultured Rat Sertoli Cells

Auzanneau

Thoreau

Kitzis

et al. 2003

Journal of Biological Chemistry

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Sertoli cells from mammalian testis are key cells involved in development and maintenance of stem cell spermatogonia as well as secretion of a chloride-and potassium-rich fluid into the lumen of seminiferous tubules. Using whole-cell patch clamp experiments, a novel chloride current was identified. It is activated only in the presence of an extracellular acidic pH, with an estimated half-maximal activation at pH 5.5. The current is strongly outwardly rectifying, activated with a fast time-dependent onset of activation but a slow timedependent kinetic at depolarization pulses. The pH-activated chloride current was not detected at physiological or basic pH and is not sensitive to intracellular or extracellular Ca 2؉ variation. Diphenylamine-2-carboxylic acid and 4,4-diisothiocyanatostilbene-2,2-disulfonic acid blocked the induced currents, and its anionic selectivity sequence was Cl ؊ > Br ؊ > I ؊ > gluconate. We have performed a reverse transcription-PCR analysis to search for voltage-dependent chloride rClC channels in cultured rat Sertoli cells. Among the nine members of the family only rClC-2, rClC-3, rClC-6, and rClC-7 have been identified. The inwardly rectifying rClC-2 chloride current was activated by hyperpolarization but not by pH variation. A different depolarization-activated outwardly rectifying chloride current was activated only by hypotonic challenge and may correspond either to rClC-3 or rClC-6. Immunolocalization experiments demonstrate that rClC-7 resides in the intracellular compartment of Sertoli cells. This study provides the first functional identification of a native acid-activated chloride current. Based on our molecular analysis of rClC proteins, this new chloride current does not correspond to rClC-2, rClC-3, rClC-6, or rClC-7 channels. The potential physiological role of this native current in an epithelial cell from the reproductive system is discussed.

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Inflammatory mediators increase surface expression of integrin ligands, adhesion to lymphocytes, and secretion of interleukin 6 in mouse Sertoli cells.

Cited by 98 publications

References 40 publications

Intercellular adhesion molecule-1 is a regulator of blood–testis barrier function

Intercellular adhesion molecule-1 is a regulator of blood–testis barrier function

TNF-α and IFN-γ Regulate Expression and Function of the Fas System in the Seminiferous Epithelium

A Novel Voltage-dependent Chloride Current Activated by Extracellular Acidic pH in Cultured Rat Sertoli Cells

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