Regulation of 1,25-dihydroxyvitamin D3 production by cultured alveolar macrophages from normal human donors and from patients with pulmonary sarcoidosis.
Identifieur interne : 000576 ( PubMed/Corpus ); précédent : 000575; suivant : 000577Regulation 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.
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
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<record><TEI><teiHeader><fileDesc><titleStmt><title xml:lang="en">Regulation of 1,25-dihydroxyvitamin D3 production by cultured alveolar macrophages from normal human donors and from patients with pulmonary sarcoidosis.</title><author><name sortKey="Reichel, H" sort="Reichel, H" uniqKey="Reichel H" first="H" last="Reichel">H. Reichel</name><affiliation><nlm:affiliation>Department of Biochemistry, University of California, Riverside 92521.</nlm:affiliation></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></titleStmt><publicationStmt><idno type="wicri:source">PubMed</idno><date when="1987">1987</date><idno type="RBID">pubmed:3119653</idno><idno type="pmid">3119653</idno><idno type="doi">10.1210/jcem-65-6-1201</idno><idno type="wicri:Area/PubMed/Corpus">000576</idno><idno type="wicri:explorRef" wicri:stream="PubMed" wicri:step="Corpus" wicri:corpus="PubMed">000576</idno></publicationStmt><sourceDesc><biblStruct><analytic><title xml:lang="en">Regulation of 1,25-dihydroxyvitamin D3 production by cultured alveolar macrophages from normal human donors and from patients with pulmonary sarcoidosis.</title><author><name sortKey="Reichel, H" sort="Reichel, H" uniqKey="Reichel H" first="H" last="Reichel">H. Reichel</name><affiliation><nlm:affiliation>Department of Biochemistry, University of California, Riverside 92521.</nlm:affiliation></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="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="drug effects" xml:lang="en"><term>Macrophages</term></keywords><keywords scheme="MESH" qualifier="physiology" xml:lang="en"><term>Macrophages</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></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><pubmed><MedlineCitation Status="MEDLINE" Owner="NLM"><PMID Version="1">3119653</PMID><DateCompleted><Year>1988</Year><Month>01</Month><Day>14</Day></DateCompleted><DateRevised><Year>2013</Year><Month>11</Month><Day>21</Day></DateRevised><Article PubModel="Print"><Journal><ISSN IssnType="Print">0021-972X</ISSN><JournalIssue CitedMedium="Print"><Volume>65</Volume><Issue>6</Issue><PubDate><Year>1987</Year><Month>Dec</Month></PubDate></JournalIssue><Title>The Journal of clinical endocrinology and metabolism</Title><ISOAbbreviation>J. Clin. Endocrinol. Metab.</ISOAbbreviation></Journal><ArticleTitle>Regulation of 1,25-dihydroxyvitamin D3 production by cultured alveolar macrophages from normal human donors and from patients with pulmonary sarcoidosis.</ArticleTitle><Pagination><MedlinePgn>1201-9</MedlinePgn></Pagination><Abstract><AbstractText>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.</AbstractText></Abstract><AuthorList CompleteYN="Y"><Author ValidYN="Y"><LastName>Reichel</LastName><ForeName>H</ForeName><Initials>H</Initials><AffiliationInfo><Affiliation>Department of Biochemistry, University of California, Riverside 92521.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Koeffler</LastName><ForeName>H P</ForeName><Initials>HP</Initials></Author><Author ValidYN="Y"><LastName>Barbers</LastName><ForeName>R</ForeName><Initials>R</Initials></Author><Author ValidYN="Y"><LastName>Norman</LastName><ForeName>A W</ForeName><Initials>AW</Initials></Author></AuthorList><Language>eng</Language><GrantList CompleteYN="N"><Grant><GrantID>AM-14,750</GrantID><Acronym>AM</Acronym><Agency>NIADDK NIH HHS</Agency><Country>United States</Country></Grant><Grant><GrantID>CA-26,038</GrantID><Acronym>CA</Acronym><Agency>NCI NIH HHS</Agency><Country>United States</Country></Grant><Grant><GrantID>CA-33,936</GrantID><Acronym>CA</Acronym><Agency>NCI NIH HHS</Agency><Country>United States</Country></Grant></GrantList><PublicationTypeList><PublicationType UI="D016428">Journal Article</PublicationType><PublicationType UI="D013485">Research Support, Non-U.S. Gov't</PublicationType><PublicationType UI="D013487">Research Support, U.S. Gov't, P.H.S.</PublicationType></PublicationTypeList></Article><MedlineJournalInfo><Country>United States</Country><MedlineTA>J Clin Endocrinol Metab</MedlineTA><NlmUniqueID>0375362</NlmUniqueID><ISSNLinking>0021-972X</ISSNLinking></MedlineJournalInfo><ChemicalList><Chemical><RegistryNumber>0</RegistryNumber><NameOfSubstance UI="D008070">Lipopolysaccharides</NameOfSubstance></Chemical><Chemical><RegistryNumber>7S5I7G3JQL</RegistryNumber><NameOfSubstance UI="D003907">Dexamethasone</NameOfSubstance></Chemical><Chemical><RegistryNumber>82115-62-6</RegistryNumber><NameOfSubstance UI="D007371">Interferon-gamma</NameOfSubstance></Chemical><Chemical><RegistryNumber>886U3H6UFF</RegistryNumber><NameOfSubstance UI="D002738">Chloroquine</NameOfSubstance></Chemical><Chemical><RegistryNumber>FXC9231JVH</RegistryNumber><NameOfSubstance UI="D002117">Calcitriol</NameOfSubstance></Chemical></ChemicalList><CitationSubset>AIM</CitationSubset><CitationSubset>IM</CitationSubset><MeshHeadingList><MeshHeading><DescriptorName UI="D000328" MajorTopicYN="N">Adult</DescriptorName></MeshHeading><MeshHeading><DescriptorName UI="D002117" MajorTopicYN="N">Calcitriol</DescriptorName><QualifierName UI="Q000096" MajorTopicYN="Y">biosynthesis</QualifierName><QualifierName UI="Q000494" MajorTopicYN="N">pharmacology</QualifierName></MeshHeading><MeshHeading><DescriptorName UI="D002478" MajorTopicYN="N">Cells, Cultured</DescriptorName></MeshHeading><MeshHeading><DescriptorName UI="D002738" MajorTopicYN="N">Chloroquine</DescriptorName><QualifierName UI="Q000494" MajorTopicYN="N">pharmacology</QualifierName></MeshHeading><MeshHeading><DescriptorName UI="D003907" MajorTopicYN="N">Dexamethasone</DescriptorName><QualifierName UI="Q000494" MajorTopicYN="N">pharmacology</QualifierName></MeshHeading><MeshHeading><DescriptorName UI="D006801" MajorTopicYN="N">Humans</DescriptorName></MeshHeading><MeshHeading><DescriptorName UI="D007371" MajorTopicYN="N">Interferon-gamma</DescriptorName><QualifierName UI="Q000494" MajorTopicYN="N">pharmacology</QualifierName></MeshHeading><MeshHeading><DescriptorName UI="D008070" MajorTopicYN="N">Lipopolysaccharides</DescriptorName><QualifierName UI="Q000494" MajorTopicYN="N">pharmacology</QualifierName></MeshHeading><MeshHeading><DescriptorName UI="D008171" MajorTopicYN="N">Lung Diseases</DescriptorName><QualifierName UI="Q000503" MajorTopicYN="Y">physiopathology</QualifierName></MeshHeading><MeshHeading><DescriptorName UI="D008264" MajorTopicYN="N">Macrophages</DescriptorName><QualifierName UI="Q000187" 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