PMID- 15606616
OWN - NLM
STAT- MEDLINE
DCOM- 20050302
LR  - 20220317
IS  - 0009-9104 (Print)
IS  - 1365-2249 (Electronic)
IS  - 0009-9104 (Linking)
VI  - 139
IP  - 1
DP  - 2005 Jan
TI  - The beneficial effects of treatment with all-trans-retinoic acid plus 
      corticosteroid on autoimmune nephritis in NZB/WF mice.
PG  - 74-83
AB  - Corticosteroids are highly effective anti-inflammatory or immunosuppressive drugs 
      used commonly to treat human systemic lupus erythematosus (SLE). 
      All-trans-retinoic acid (ATRA), which belongs to a class of retinoids that exert 
      immunomodulatory and anti-inflammatory functions, can also suppress the 
      development of lupus nephritis in an animal model. However, both agents can 
      inflict serious adverse effects. Here, we have asked whether ATRA can serve as a 
      steroid-sparing drug in the treatment of lupus nephritis. To examine the efficacy 
      of combining predonisolone (PSL) with ATRA, we treated intraperitoneally New 
      Zealand black/white F1 (NZB/W F1) mice with PSL, ATRA or both agents. Survival 
      rate and proteinuria were determined once a month. Cytokine and anti-DNA antibody 
      production were determined by enzyme-linked immunosorbent assay (ELISA) and 
      reverse transcription-polymerase chain reaction (RT-PCR). Renal histopathology 
      was observed by haematoxylin and periodic acid Schiff (PAS), immunoperoxidase and 
      immunohistochemical assay. Survival rate and proteinuria were improved in all 
      experimental groups, and were much improved in the mice receiving the combination 
      of ATRA and PSL (P <0.05). A single administration of ATRA reduced the Th1 
      [interleukin (IL)-2, interferon (IFN)-gamma and IL-12], and a Th2 (IL-4) cytokine 
      level, as effectively as administration of PSL. ATRA also suppressed the 
      expression of inducible nitric oxide synthetase (iNOS) and monocyte 
      chemoattractant protein-1 (MCP-1) in the kidney. The combination of PSL and ATRA 
      significantly reduced IgG2 (especially IgG2b)-specific anti-DNA antibody levels 
      in comparison with administration of either agent alone. These data suggest that 
      ATRA might have the potential to act as a new therapeutic and steroid-sparing 
      drug against lupus nephritis.
FAU - Nozaki, Y
AU  - Nozaki Y
AD  - Department of Hematology, Nephrology and Rheumatology, Kinki University School of 
      Medicine, Osaka, Japan. nozaki@int3.med.kindai.ac.jp
FAU - Yamagata, T
AU  - Yamagata T
FAU - Yoo, B-S
AU  - Yoo BS
FAU - Sugiyama, M
AU  - Sugiyama M
FAU - Ikoma, S
AU  - Ikoma S
FAU - Kinoshita, K
AU  - Kinoshita K
FAU - Funauchi, M
AU  - Funauchi M
FAU - Kanamaru, A
AU  - Kanamaru A
LA  - eng
PT  - Journal Article
PL  - England
TA  - Clin Exp Immunol
JT  - Clinical and experimental immunology
JID - 0057202
RN  - 0 (Anti-Inflammatory Agents)
RN  - 0 (Antibodies, Antinuclear)
RN  - 0 (Ccl2 protein, mouse)
RN  - 0 (Chemokine CCL2)
RN  - 0 (Cytokines)
RN  - 0 (Glucocorticoids)
RN  - 0 (Immunoglobulin G)
RN  - 0 (Keratolytic Agents)
RN  - 0 (RNA, Messenger)
RN  - 5688UTC01R (Tretinoin)
RN  - 9007-49-2 (DNA)
RN  - 9PHQ9Y1OLM (Prednisolone)
RN  - EC 1.14.13.39 (Nitric Oxide Synthase)
RN  - EC 1.14.13.39 (Nitric Oxide Synthase Type II)
RN  - EC 1.14.13.39 (Nos2 protein, mouse)
SB  - IM
MH  - Animals
MH  - Anti-Inflammatory Agents/*therapeutic use
MH  - Antibodies, Antinuclear/blood
MH  - Body Weight/drug effects
MH  - Chemokine CCL2/immunology
MH  - Cytokines/blood/immunology
MH  - DNA/immunology
MH  - Drug Therapy, Combination
MH  - Female
MH  - Glucocorticoids/*therapeutic use
MH  - Immunoglobulin G/analysis
MH  - Immunohistochemistry/methods
MH  - Keratolytic Agents/therapeutic use
MH  - Kidney/immunology/pathology
MH  - Lupus Nephritis/blood/*drug therapy/mortality
MH  - Mice
MH  - Mice, Inbred NZB
MH  - Nitric Oxide Synthase/immunology
MH  - Nitric Oxide Synthase Type II
MH  - Prednisolone/*therapeutic use
MH  - Proteinuria/drug therapy
MH  - RNA, Messenger/analysis
MH  - Spleen/drug effects
MH  - Tretinoin/*therapeutic use
PMC - PMC1809273
EDAT- 2004/12/21 09:00
MHDA- 2005/03/03 09:00
PMCR- 2006/01/01
CRDT- 2004/12/21 09:00
PHST- 2004/12/21 09:00 [pubmed]
PHST- 2005/03/03 09:00 [medline]
PHST- 2004/12/21 09:00 [entrez]
PHST- 2006/01/01 00:00 [pmc-release]
AID - CEI2654 [pii]
AID - 10.1111/j.1365-2249.2005.02654.x [doi]
PST - ppublish
SO  - Clin Exp Immunol. 2005 Jan;139(1):74-83. doi: 10.1111/j.1365-2249.2005.02654.x.