Regulation of 1,25-dihydroxyvitamin D3 production by cultured alveolar macrophages from normal human donors and from patients with pulmonary sarcoidosis.
Identifieur interne : 003269 ( Main/Exploration ); précédent : 003268; suivant : 003270Regulation of 1,25-dihydroxyvitamin D3 production by cultured alveolar macrophages from normal human donors and from patients with pulmonary sarcoidosis.
Auteurs : H. Reichel ; H P Koeffler ; R. Barbers ; A W NormanSource :
- The Journal of clinical endocrinology and metabolism [ 0021-972X ] ; 1987.
Descripteurs français
- KwdFr :
- Adulte, Adulte d'âge moyen, Alvéoles pulmonaires, Calcitriol (biosynthèse), Calcitriol (pharmacologie), Cellules cultivées, Chloroquine (pharmacologie), Dexaméthasone (pharmacologie), Humains, Interféron gamma (pharmacologie), Lipopolysaccharides (pharmacologie), Macrophages (), Macrophages (physiologie), Macrophages (physiopathologie), Maladies pulmonaires (physiopathologie), Sarcoïdose (physiopathologie).
- MESH :
- biosynthèse : Calcitriol.
- pharmacologie : Calcitriol, Chloroquine, Dexaméthasone, Interféron gamma, Lipopolysaccharides.
- physiologie : Macrophages.
- physiopathologie : Macrophages, Maladies pulmonaires, Sarcoïdose.
- Adulte, Adulte d'âge moyen, Alvéoles pulmonaires, Cellules cultivées, Humains, Macrophages.
English descriptors
- KwdEn :
- Adult, Calcitriol (biosynthesis), Calcitriol (pharmacology), Cells, Cultured, Chloroquine (pharmacology), Dexamethasone (pharmacology), Humans, Interferon-gamma (pharmacology), Lipopolysaccharides (pharmacology), Lung Diseases (physiopathology), Macrophages (drug effects), Macrophages (physiology), Macrophages (physiopathology), Middle Aged, Pulmonary Alveoli, Sarcoidosis (physiopathology).
- MESH :
- chemical , biosynthesis : Calcitriol.
- chemical , pharmacology : Calcitriol, Chloroquine, Dexamethasone, Interferon-gamma, Lipopolysaccharides.
- drug effects : Macrophages.
- physiology : Macrophages.
- physiopathology : Lung Diseases, Macrophages, Sarcoidosis.
- Adult, Cells, Cultured, Humans, Middle Aged, Pulmonary Alveoli.
Abstract
Regulation of the production of the biologically active vitamin D3 sterol 1,25-dihydroxyvitamin D3 [1,25-(OH)2D3] by cultured pulmonary alveolar macrophages (PAM) obtained from 6 patients with pulmonary sarcoidosis and from 9 normal subjects was studied. The sarcoid cells, all collected from patients with normal calcium metabolism, synthesized 1,25-(OH)2-[3H]D3 from the substrate 25-hydroxyvitamin [3H]D3 (25OH-[3H]D3), whereas in vitro incubation with recombinant human interferon-gamma (IFN gamma) or lipopolysaccharide (LPS) was required for induction of synthesis of the hormone by normal PAM. Exogenous 1,25-(OH)2D3 (10-100 nmol/L) decreased endogenous hormone production by normal PAM by approximately 45%. The relative inhibitory effect of 1,25-(OH)2D3 was less pronounced in sarcoid PAM, in which 10-100 nmol/L 1,25-(OH)2D3 inhibited 250HD3-1-hydroxylase by approximately 25%. An accompanying induction of the 250HD3-24-hydroxylase, which is typical for renal cells, was found at low levels in only 3 of 10 experiments; in this regard, no differences between sarcoid and normal PAM were apparent. PTH or forskolin did not influence 250HD3 metabolism by PAM. 1,25-(OH)2D3 production by sarcoid PAM was enhanced by lipopolysaccharide and IFN gamma. Likewise, recombinant human interleukin-2 stimulated 1,25-(OH)2D3 production by sarcoid PAM, suggesting a possible role for both IFN gamma and interleukin-2 in the induction of 1,25-(OH)2D3 synthesis by sarcoid PAM in vivo. Recombinant human IFN alpha, IFN beta, and granulocyte-macrophage colony-stimulating factor had little effect. Dexamethasone and chloroquine, which have in vivo antihypercalcemic activity in sarcoidosis, both inhibited 1,25-(OH)2D3 synthesis by sarcoid PAM; chloroquine simultaneously stimulated the 24-hydroxylase. Our studies suggest that the 250HD3-metabolizing system in PAM is in some respects different from renal metabolism of 250HD3.
DOI: 10.1210/jcem-65-6-1201
PubMed: 3119653
Affiliations:
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Le document en format XML
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Reichel</name><affiliation><nlm:affiliation>Department of Biochemistry, University of California, Riverside 92521.</nlm:affiliation><wicri:noCountry code="subField">Riverside 92521</wicri:noCountry></affiliation></author><author><name sortKey="Koeffler, H P" sort="Koeffler, H P" uniqKey="Koeffler H" first="H P" last="Koeffler">H P Koeffler</name></author><author><name sortKey="Barbers, R" sort="Barbers, R" uniqKey="Barbers R" first="R" last="Barbers">R. Barbers</name></author><author><name sortKey="Norman, A W" sort="Norman, A W" uniqKey="Norman A" first="A W" last="Norman">A W Norman</name></author></analytic><series><title level="j">The Journal of clinical endocrinology and metabolism</title><idno type="ISSN">0021-972X</idno><imprint><date when="1987" type="published">1987</date></imprint></series></biblStruct></sourceDesc></fileDesc><profileDesc><textClass><keywords scheme="KwdEn" xml:lang="en"><term>Adult</term><term>Calcitriol (biosynthesis)</term><term>Calcitriol (pharmacology)</term><term>Cells, Cultured</term><term>Chloroquine (pharmacology)</term><term>Dexamethasone (pharmacology)</term><term>Humans</term><term>Interferon-gamma (pharmacology)</term><term>Lipopolysaccharides (pharmacology)</term><term>Lung Diseases (physiopathology)</term><term>Macrophages (drug effects)</term><term>Macrophages (physiology)</term><term>Macrophages (physiopathology)</term><term>Middle Aged</term><term>Pulmonary Alveoli</term><term>Sarcoidosis (physiopathology)</term></keywords><keywords scheme="KwdFr" xml:lang="fr"><term>Adulte</term><term>Adulte d'âge moyen</term><term>Alvéoles pulmonaires</term><term>Calcitriol (biosynthèse)</term><term>Calcitriol (pharmacologie)</term><term>Cellules cultivées</term><term>Chloroquine (pharmacologie)</term><term>Dexaméthasone (pharmacologie)</term><term>Humains</term><term>Interféron gamma (pharmacologie)</term><term>Lipopolysaccharides (pharmacologie)</term><term>Macrophages ()</term><term>Macrophages (physiologie)</term><term>Macrophages (physiopathologie)</term><term>Maladies pulmonaires (physiopathologie)</term><term>Sarcoïdose (physiopathologie)</term></keywords><keywords scheme="MESH" type="chemical" qualifier="biosynthesis" xml:lang="en"><term>Calcitriol</term></keywords><keywords scheme="MESH" type="chemical" qualifier="pharmacology" xml:lang="en"><term>Calcitriol</term><term>Chloroquine</term><term>Dexamethasone</term><term>Interferon-gamma</term><term>Lipopolysaccharides</term></keywords><keywords scheme="MESH" qualifier="biosynthèse" xml:lang="fr"><term>Calcitriol</term></keywords><keywords scheme="MESH" qualifier="drug effects" xml:lang="en"><term>Macrophages</term></keywords><keywords scheme="MESH" qualifier="pharmacologie" xml:lang="fr"><term>Calcitriol</term><term>Chloroquine</term><term>Dexaméthasone</term><term>Interféron gamma</term><term>Lipopolysaccharides</term></keywords><keywords scheme="MESH" qualifier="physiologie" xml:lang="fr"><term>Macrophages</term></keywords><keywords scheme="MESH" qualifier="physiology" xml:lang="en"><term>Macrophages</term></keywords><keywords scheme="MESH" qualifier="physiopathologie" xml:lang="fr"><term>Macrophages</term><term>Maladies pulmonaires</term><term>Sarcoïdose</term></keywords><keywords scheme="MESH" qualifier="physiopathology" xml:lang="en"><term>Lung Diseases</term><term>Macrophages</term><term>Sarcoidosis</term></keywords><keywords scheme="MESH" xml:lang="en"><term>Adult</term><term>Cells, Cultured</term><term>Humans</term><term>Middle Aged</term><term>Pulmonary Alveoli</term></keywords><keywords scheme="MESH" xml:lang="fr"><term>Adulte</term><term>Adulte d'âge moyen</term><term>Alvéoles pulmonaires</term><term>Cellules cultivées</term><term>Humains</term><term>Macrophages</term></keywords></textClass></profileDesc></teiHeader><front><div type="abstract" xml:lang="en">Regulation of the production of the biologically active vitamin D3 sterol 1,25-dihydroxyvitamin D3 [1,25-(OH)2D3] by cultured pulmonary alveolar macrophages (PAM) obtained from 6 patients with pulmonary sarcoidosis and from 9 normal subjects was studied. The sarcoid cells, all collected from patients with normal calcium metabolism, synthesized 1,25-(OH)2-[3H]D3 from the substrate 25-hydroxyvitamin [3H]D3 (25OH-[3H]D3), whereas in vitro incubation with recombinant human interferon-gamma (IFN gamma) or lipopolysaccharide (LPS) was required for induction of synthesis of the hormone by normal PAM. Exogenous 1,25-(OH)2D3 (10-100 nmol/L) decreased endogenous hormone production by normal PAM by approximately 45%. The relative inhibitory effect of 1,25-(OH)2D3 was less pronounced in sarcoid PAM, in which 10-100 nmol/L 1,25-(OH)2D3 inhibited 250HD3-1-hydroxylase by approximately 25%. An accompanying induction of the 250HD3-24-hydroxylase, which is typical for renal cells, was found at low levels in only 3 of 10 experiments; in this regard, no differences between sarcoid and normal PAM were apparent. PTH or forskolin did not influence 250HD3 metabolism by PAM. 1,25-(OH)2D3 production by sarcoid PAM was enhanced by lipopolysaccharide and IFN gamma. Likewise, recombinant human interleukin-2 stimulated 1,25-(OH)2D3 production by sarcoid PAM, suggesting a possible role for both IFN gamma and interleukin-2 in the induction of 1,25-(OH)2D3 synthesis by sarcoid PAM in vivo. Recombinant human IFN alpha, IFN beta, and granulocyte-macrophage colony-stimulating factor had little effect. Dexamethasone and chloroquine, which have in vivo antihypercalcemic activity in sarcoidosis, both inhibited 1,25-(OH)2D3 synthesis by sarcoid PAM; chloroquine simultaneously stimulated the 24-hydroxylase. Our studies suggest that the 250HD3-metabolizing system in PAM is in some respects different from renal metabolism of 250HD3.</div></front></TEI><affiliations><list></list><tree><noCountry><name sortKey="Barbers, R" sort="Barbers, R" uniqKey="Barbers R" first="R" last="Barbers">R. Barbers</name><name sortKey="Koeffler, H P" sort="Koeffler, H P" uniqKey="Koeffler H" first="H P" last="Koeffler">H P Koeffler</name><name sortKey="Norman, A W" sort="Norman, A W" uniqKey="Norman A" first="A W" last="Norman">A W Norman</name><name sortKey="Reichel, H" sort="Reichel, H" uniqKey="Reichel H" first="H" last="Reichel">H. Reichel</name></noCountry></tree></affiliations></record>Pour manipuler ce document sous Unix (Dilib)
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