Retinoic acid inhibits the regulated expression of vascular cell adhesion molecule-1 by cultured dermal microvascular endothelial cells.

Gille, Jens; Paxton, Lani L.L.; Lawley, T J; Caughman, S. Wright; Swerlick, RA

doi:10.1172/jci119184

Cited by 79 publications

(46 citation statements)

References 44 publications

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“…These data are in line with a previous report demonstrating RA-mediated suppression of VCAM-1 by EC [23], supporting the concept that ATRA may inhibit the extravasating capacity of leukocytes through action at the level of both the monocyte and the EC. Since macrophages are known to increase in number and/or to be functionally altered in several diseases [19][20][21][22], inhibition of monocyte extravasation (along with their diminished survival [9]) could help lower monocyte triggered inflammation in these settings.…”

Section: Discussionsupporting

confidence: 92%

“…in rheumatoid arthritis and inflammatory bowel disease, and also to be relevant to other pathological conditions such as tumor angiogenesis and dysregulated renal development [19][20][21][22]. Based on the role of ATRA to interfere with the expression of adhesion molecules by EC [23], we hypothesized that this effect may be amplified by an analogous alteration at the leukocyte surface. We report here that this is the case with ATRA affecting selectively the expression of integrins on blood derived monocytes.…”

Section: Introductionmentioning

confidence: 99%

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All‐trans retinoic acid down‐regulates expression and function of β₂ integrins by human monocytes: opposite effects on monocytic cell lines

Babina

Henz

2003

Eur J Immunol

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All-trans retinoic acid (ATRA) plays an important role in the differentiation of malignant myeloid cells but its effects on primary leukocytes have been poorly investigated. We report here that ATRA negatively affects expression and function of leukocyte integrins that play a key role in monocyte adhesive interactions. As evidenced by flow cytometry, ATRA (at 1 ? M) clearly and donor-independently suppressed the expression of all integrin chains investigated (CD11a, CD11b, CD11c, and CD18), most strikingly of CD11a. Down-regulation was detectable after 24 and maximal after 72-96 h. Reverse transcription-PCR analysis revealed diminished steady-state concentrations of § specific transcripts but not of the common g chain, suggesting that heterodimer expression was predominantly regulated through § chains. Results obtained with blood-derived monocytes were in sharp contrast to those for the leukemic cell lines THP-1 and U937, both of which showed marked increase in all integrin subunits in response to ATRA. ATRA-pretreated monocytes displayed significantly diminished g 2 integrin-dependent homotypic aggregation, and adhesion to stimulated endothelial cells (EC), while ATRA-pretreated monocytic cell lines showed the opposite behavior displaying markedly enhanced aggregation and CD18-mediated adhesion to EC. Therefore, the level of leukocyte integrins was obviously a decisive factor for these adhesive interactions irrespective of the cellular source. Collectively, our data indicate a striking difference between leukemic cell lines and normal hematopoietic cells with regard to ATRA responsiveness. By acting on key adhesive structures of normal leukocytes, ATRA mediates processes that may be of substantially broad range applying to inflammation and immunity in addition to differentiation and proliferation.

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Section: Discussionsupporting

confidence: 92%

Section: Introductionmentioning

confidence: 99%

All‐trans retinoic acid down‐regulates expression and function of β₂ integrins by human monocytes: opposite effects on monocytic cell lines

Babina

Henz

2003

Eur J Immunol

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“…When the NF-B pathway is activated by agents such as lipopolysaccharide, IL-1␤, and TNF-␣, a phosphorylation-dependent proteolytic degradation of I-B is initiated, allowing NF-B to translocate into the nucleus (Baldwin, 1996). In HUV, it has been proposed that NF-B is involved in the expression of BK B 1 receptor-mediated contractions after a prolonged in vitro incubation (Sardi et al, , 2000b, since these responses are inhibited by continuous exposure to agents with NF-B pathway inhibitory activity such as PDTC, dexamethasone, or retinoids (Traenckner et al, 1994;Gille et al, 1997;Ni et al, 1998). Pierce et al (1997) have reported that Bay 11-7082 prevents I-B phosphorylation as well as its subsequent degradation, thus inhibiting NF-B activation.…”

Section: Discussionmentioning

confidence: 99%

Further Pharmacological Evidence of Nuclear Factor-κB Pathway Involvement in Bradykinin B₁Receptor-Sensitized Responses in Human Umbilical Vein

Sardi

Rey-Ares²,

Pujol-Lereis³

et al. 2002

J Pharmacol Exp Ther

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Bradykinin (BK) B 1 receptors are thought to exert a pivotal role in maintaining and modulating inflammatory processes. They are not normally present under physiological situations but are induced under physiopathological conditions. In isolated human umbilical vein (HUV), a spontaneous BK B 1 receptor upregulation and sensitization process has been demonstrated. Based on pyrrolidine-dithiocarbamate inhibition, it has been proposed that this phenomenon is dependent on nuclear factor-B (NF-B) activation. The aim of this study was to further evaluate the NF-B pathway involvement on BK B 1 receptor sensitization in isolated HUV, using several pharmacological tools. In 5-h incubated rings, either the I-B kinase inhibitor 3-(4-methylphenylsulfonyl)-2-propenenitrile or the proteasome activity inhibitor Z-Leu-Leu-Leu-CHO (MG-132) inhibited the development of the BK B 1 receptorsensitized contractile responses. Furthermore, pro-inflammatory cytokine interleukin-6 (IL-6) produced a leftward shift of the concentration-response curve to the BK B 1 receptor agonist, whereas anti-inflammatory cytokines interleukin-4 (IL-4) and tumor growth factor-␤1 (TGF-␤1) produced a rightward shift of the responses to des-Arg 9 -BK in our preparations. Taken together, these results point to NF-B as a key intermediary in the activation of the expression of BK B 1 receptor-sensitized responses in HUV and support the role of inflammatory mediators in the modulation of this process.

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“…The VCAM-1 promoter contains several potential transcription factor-binding sites, of which NF-B, GATA, IRF-1, AP-1, and SP1 have been implicated in induction of VCAM-1 gene transcription in response to various pro-inflammatory stimuli, including TNF␣, lipopolysaccharide and cytokines (47,(55)(56)(57)(58). In the present study, we used reporter gene assays to investigate the effect of rhinovirus infection on VCAM-1 promoter activity and observed that rhinovirus infection of A549 epithelial cells strongly induced VCAM-1 promoter activity.…”

Section: The Gata-binding Sites Within the Region ϫ258/ϫ98 And The Nfmentioning

confidence: 99%

Respiratory Epithelial Cell Expression of Vascular Cell Adhesion Molecule-1 and Its Up-regulation by Rhinovirus Infection via NF-κB and GATA Transcription Factors

Papi

Johnston

1999

Journal of Biological Chemistry

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Virus infections, the majority of which are rhinovirus infections, are the major cause of asthma exacerbations. Asthma now affects one-fifth of the population, yet treatment of exacerbations is unsatisfactory, and the pathogenesis is unclear. Intraepithelial lymphocyte and eosinophil infiltration and activation are strongly implicated, but the mechanisms regulating these processes are unknown. We hypothesized that lower airway epithelial expression of vascular cell adhesion molecule-1 (VCAM-1) may be important in intraepithelial inflammation and that expression would be induced by pro-inflammatory stimuli and rhinovirus infection. We investigated respiratory epithelial cell VCAM-1 expression and its regulation to identify new targets for treatment of virus-induced asthma exacerbations. We observed constitutive respiratory epithelial cell VCAM-1 expression and that rhinovirus infection, but no other pro-inflammatory stimuli tested increased VCAM-1 cell surface expression in respiratory epithelial cell lines and primary bronchial epithelial cells. We then observed rhinovirus induction of VCAM-1 mRNA expression, promoter activity, and mRNA transcription. Rhinovirus induction of VCAM-1 promoter activity was critically dependent on up-regulation of proteins binding to the ؊254/؊251 and ؊239/؊236 GATA-binding sites and to the ؊72/؊63 and ؊57/؊48 NF-B-binding sites in the VCAM-1 promoter. These studies identify VCAM-1 and the NF-B and GATA transcription factor families as new targets for development of therapeutic interventions for virus-induced asthma exacerbations.

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Retinoic acid inhibits the regulated expression of vascular cell adhesion molecule-1 by cultured dermal microvascular endothelial cells.

Abstract: The

Cited by 79 publications

References 44 publications

All‐trans retinoic acid down‐regulates expression and function of β₂ integrins by human monocytes: opposite effects on monocytic cell lines

All‐trans retinoic acid down‐regulates expression and function of β₂ integrins by human monocytes: opposite effects on monocytic cell lines

Further Pharmacological Evidence of Nuclear Factor-κB Pathway Involvement in Bradykinin B₁Receptor-Sensitized Responses in Human Umbilical Vein

Respiratory Epithelial Cell Expression of Vascular Cell Adhesion Molecule-1 and Its Up-regulation by Rhinovirus Infection via NF-κB and GATA Transcription Factors

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Retinoic acid inhibits the regulated expression of vascular cell adhesion molecule-1 by cultured dermal microvascular endothelial cells.

Abstract: The

Cited by 79 publications

References 44 publications

All‐trans retinoic acid down‐regulates expression and function of β2 integrins by human monocytes: opposite effects on monocytic cell lines

All‐trans retinoic acid down‐regulates expression and function of β2 integrins by human monocytes: opposite effects on monocytic cell lines

Further Pharmacological Evidence of Nuclear Factor-κB Pathway Involvement in Bradykinin B1Receptor-Sensitized Responses in Human Umbilical Vein

Respiratory Epithelial Cell Expression of Vascular Cell Adhesion Molecule-1 and Its Up-regulation by Rhinovirus Infection via NF-κB and GATA Transcription Factors

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All‐trans retinoic acid down‐regulates expression and function of β₂ integrins by human monocytes: opposite effects on monocytic cell lines

All‐trans retinoic acid down‐regulates expression and function of β₂ integrins by human monocytes: opposite effects on monocytic cell lines

Further Pharmacological Evidence of Nuclear Factor-κB Pathway Involvement in Bradykinin B₁Receptor-Sensitized Responses in Human Umbilical Vein