Downregulation of TGF-beta1 mRNA and protein in the muscles of patients with inflammatory myopathies after treatment with high-dose intravenous immunoglobulin.
We used reverse transcription-polymerase chain reaction to study the level of TGF-beta1 mRNA expression and immunocytochemistry to examine the immunoreactive TGF-beta1 in muscle biopsy specimens from five patients with dermatomyositis (DM) and five patients with inclusion body myositis (IBM) obtained before and after 3 months treatment with intravenous immunoglobulin (IVIg). At baseline, the mRNA expression of TGF-beta1 was increased up to fivefold in the muscles of DM patients compared to that of IBM patients. After IVIg, TGF-beta1 was downregulated and the TGF-beta1 mRNA decreased twofold in the muscles of patients with DM who had successfully responded to therapy, but remained unchanged in the muscles of patients with IBM who did not respond. The downregulation of TGF-beta1 in DM was associated with improvement of the muscle cytoarchitecture and reduction of the endomysial inflammation and connective tissue, suggesting that in DM the excess of TGF-beta1 may be involved in the pathogenesis of chronic inflammation, fibrosis, and accumulation of extracellular matrix proteins.
Amemiya
K
K
Neuromuscular Diseases Section, National Institutes of Health, Bethesda, Maryland 20892, USA.
Semino-Mora
C
C
Granger
R P
RP
Dalakas
M C
MC
D000328:Adult; D003882:Dermatomyositis / Q000188:drug therapy* / Q000235:genetics / Q000378:metabolism; D005260:Female; D005987:Glyceraldehyde-3-Phosphate Dehydrogenases / Q000235:genetics / Q000378:metabolism*; D006801:Humans; D016756:Immunoglobulins, Intravenous / Q000627:therapeutic use*; D007150:Immunohistochemistry; D008875:Middle Aged; D009132:Muscles / Q000378:metabolism* / Q000473:pathology; D018979:Myositis, Inclusion Body / Q000188:drug therapy / Q000235:genetics / Q000378:metabolism; D012333:RNA, Messenger / Q000378:metabolism; D020133:Reverse Transcriptase Polymerase Chain Reaction; D016212:Transforming Growth Factor beta / Q000235:genetics / Q000378:metabolism*
D016756:Immunoglobulins, Intravenous; D012333:RNA, Messenger; D016212:Transforming Growth Factor beta; D005987:Glyceraldehyde-3-Phosphate Dehydrogenases