Adhesion of Immature and Mature T Cells Induces inHuman Thymic Epithelial Cells (TEC) Activation of IL‐6Gene Trascription Factors (NF‐κB And NF‐IL6) and IL‐6Gene Expression: Role of αtβ1 and α6β4 Integrins

Fiorini, Emma; Marchisio, Pier Carlo; Scupoli, Maria Teresa; Poffe, Ornella; Tagliabue, Elda; Brentegani, Monica; Colombatti, Marco; Santini, Franscesco; Tridente, Giuseppe; Ramarli, Dunia

doi:10.1155/2000/48239

Cited by 22 publications

(20 citation statements)

References 28 publications

(12 reference statements)

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Strongly expressed at the TEC surface throughout their life cycle, § 6 g 4 integrin mediates TEC-extracellular matrix (ECM) and TEC-thymocyte adhesion at the same time [11][12][13]. We here clearly demonstrate that laminin- § 6 g 4 interaction is one of the mechanisms maintaining the basal phosphorylation of p38 and hence the basal production of IL-6 as both decreased upon disruption of TEC-TEC-secreted laminin interaction by anti-laminin Ab.…”

Section: Discussionmentioning

confidence: 99%

“…Primary TEC were derived under informed consent from discarded tissue of 14 independent thymuses of patients ( X 5 years of age) undergoing cardiac surgery as previously described [11][12][13]. Secondary cultures were grown to confluence at 1/3 of medium complements and then deprived of them for 48 h. If indicated, TEC were incubated with saturating doses of the appropriate mAb (5 ?…”

Section: Culture and Treatment Of Tecmentioning

confidence: 99%

“…Nuclear and cytoplasmic extracts were prepared from TEC as previously described [11][12][13]. Protein amount was measured by Coomassie protein assay reagent (Pierce, Rockford, IL).…”

Section: Cell Extracts and Electrophoretic Mobility Shift Assaymentioning

confidence: 99%

“…Previous and ours results have demonstrated that (1) TEC derived from normal thymus and grown to organized monolayers, constitutively produce extracellular matrix proteins (laminins, fibronectin and collagen type IV); (2) these cells display two sets of integrins polarized at discrete locations ( § 2 g 1 and § 3 g 1 heterodimers, mostly located at the TEC-TEC boundaries, and § 6 g 4, colocalized with its ligand laminin at the base of the monolayer); and (3) thymocyte or lymphocyte adhesion remodels this pattern, so that § 6 g 4 and § 3 g 1, but not § 2 g 1 integrins, cluster also around individual lymphoid cells, recognizing yet unknown cellular ligands expressed by T cells [10][11][12][13].…”

Section: Introductionmentioning

confidence: 99%

“…We have shown that in these TEC § 6 g 4 or § 3 g 1 integrins regulate IL-6 production through signals that, elicited by thymocyte/lymphocyte adhesion or mAb cross-linking, induce NF-‹ B nuclear translocation and serine phosphorylation of active NF-IL6 isoforms (43 and 36 kDa) [11][12][13]. As § 6 g 4 integrin evoked the greatest responses, we further investigated some of the molecular mechanisms involved in its activity.…”

Section: Introductionmentioning

confidence: 99%

See 4 more Smart Citations

p38 MAPK is a critical regulator of the constitutive and the β4 integrin‐regulated expression of IL‐6 in human normal thymic epithelial cells

et al. 2003

Self Cite

View full text Add to dashboard Cite

Cytokines and adhesion receptors are key mediators in the dialog occurring between thymic epithelial cells (TEC) and thymocytes and regulating T cell maturation and epithelial embryonic differentiation. Among cytokines, IL-6 can be critical in the thymus, fostering proliferation, differentiation and/or survival of both TEC and thymocytes. We have previously reported in human normal TEC that clustering of the laminin receptor § 6 g 4 integrin induced by thymocyte contact or monoclonal antibody-mediated cross-linking regulates IL-6 gene expression via activation of NF-‹ B and NF-IL6 transactivators. Here we show that § 6 g 4 integrin activates p38 mitogen-activated protein kinase (MAPK) and that p38 is essential for IL-6 gene expression. In fact, g 4 cross-linking activated p38 and extracellular signalregulated kinase (ERK) MAPK, Rac1, p21-activated protein kinase 1 (PAK1) and MAPK kinases (MKK) 3/MKK6. However, pharmacological blockade of p38 or ERK demonstrated that p38 inhibition abrogated both basal and g 4 integrin-induced production of IL-6 preventing NF-‹ B and NF-IL6 activation, whereas ERK inhibition reduced IL-6 production, hampering only NF-‹ B activation. Overall, our results indicate that p38 MAPK and § 6 g 4 integrin, expressed by TEC throughout their life, are critical regulators of the intrathymic availability of a cytokine controlling fate and functions of cells governing development and maintenance of thymic architecture and immune responses.

show abstract

Section: Discussionmentioning

confidence: 99%

Section: Culture and Treatment Of Tecmentioning

confidence: 99%

“…Nuclear and cytoplasmic extracts were prepared from TEC as previously described [11][12][13]. Protein amount was measured by Coomassie protein assay reagent (Pierce, Rockford, IL).…”

Section: Cell Extracts and Electrophoretic Mobility Shift Assaymentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

See 3 more Smart Citations

p38 MAPK is a critical regulator of the constitutive and the β4 integrin‐regulated expression of IL‐6 in human normal thymic epithelial cells

et al. 2003

Self Cite

View full text Add to dashboard Cite

show abstract

Human MBP‐specific T cells regulate IL‐6 gene expression in astrocytes through cell–cell contacts and soluble factors

Colombatti

Moretto²,

Tommasi

et al. 2001

Glia

Self Cite

View full text Add to dashboard Cite

One of the distinctive features of multiple sclerosis (MS) attacks is homing to the CNS of activated T cells able to orchestrate humoral and cell-based events, resulting in immune-mediated injury to myelin and oligodendrocytes. Of the complex interplay occurring between T cells and CNS constituents, we have examined some aspects of T-cell interactions with astrocytes, the major components of the glial cells. Specifically, we focused on the ability of T cells to regulate the gene expression of interleukin-6 (IL-6) in astrocytes, based on previous evidence showing the involvement of this cytokine in CNS disorders. We found that T-cell adhesion and T-cell soluble factors induce IL-6 gene expression in U251 astrocytes through distinct signaling pathways, respectively, resulting in the activation of NF-kappaB and IRF-1 transcription factors. In a search for effector molecules at the astrocyte surface, we found that alpha3beta1 integrins play a role in NF-kappaB activation induced by T-cell contact, whereas interferon-gamma (IFN-gamma) receptors dominate in IRF-1 induction brought about by T-cell-derived soluble factors. Similar phenomena were observed also in normal fetal astrocyte cultures. We therefore propose that through astrocyte induction, T cells may indirectly regulate the availability of a cytokine which is crucial in modulating fate and behavior of cell populations involved in the pathogenesis of MS inflammatory lesions.

show abstract

INHIBITION OF TNF-α AND IL-6 PRODUCTION BY AUCUBIN THROUGH BLOCKADE OF NF-κB ACTIVATION IN RBL-2H3 MAST CELLS

et al. 2002

View full text Add to dashboard Cite

Adhesion of Immature and Mature T Cells Induces inHuman Thymic Epithelial Cells (TEC) Activation of IL‐6Gene Trascription Factors (NF‐κB And NF‐IL6) and IL‐6Gene Expression: Role of αtβ1 and α6β4 Integrins

Cited by 22 publications

References 28 publications

p38 MAPK is a critical regulator of the constitutive and the β4 integrin‐regulated expression of IL‐6 in human normal thymic epithelial cells

p38 MAPK is a critical regulator of the constitutive and the β4 integrin‐regulated expression of IL‐6 in human normal thymic epithelial cells

Human MBP‐specific T cells regulate IL‐6 gene expression in astrocytes through cell–cell contacts and soluble factors

INHIBITION OF TNF-α AND IL-6 PRODUCTION BY AUCUBIN THROUGH BLOCKADE OF NF-κB ACTIVATION IN RBL-2H3 MAST CELLS

Contact Info

Product

Resources

About