Leishmanial Lipid Suppresses Tumor Necrosis Factor �, Interleukin-1�, and Nitric Oxide Production by Adherent Synovial Fluid Mononuclear Cells in Rheumatoid Arthritis Patients and Induces Apoptosis Through the Mitochondrial-Mediated Pathway
IR@IICB: CSIR-Indian Institute of Chemical Biology, Kolkata
View Archive Info| Field | Value | |
| Title |
Leishmanial Lipid Suppresses Tumor Necrosis Factor �,
Interleukin-1�, and Nitric Oxide Production by
Adherent Synovial Fluid Mononuclear Cells in
Rheumatoid Arthritis Patients and Induces Apoptosis Through
the Mitochondrial-Mediated Pathway
|
|
| Creator |
Majumdar, Kajal Nayan
Banerjee, Aditi Ratha, Jagnyeswar Mandal, Mriganka Sarkar, Rathindra Nath Das Saha, Krishna |
|
| Subject |
Infectious Diseases and Immunology
|
|
| Description |
Leishmanial lipid is a strong immunosuppressor
of host cells. Inhibition of the inflammatory
responses of synovial cells through induction of apoptosis
is one of the main targets of therapeutic intervention
in rheumatoid arthritis (RA). This study was undertaken
to examine the antiinflammatory and apoptosisinducing
effects of leishmanial lipid on adherent synovial
fluid mononuclear cells (SFMCs) in patients with
RA. Lipid was extracted from a Leishmania
donovani promastigote (MHO/IN/1978/UR6) by the
Bligh and Dyer method. Nitric oxide (NO) was measured
using the Griess reaction, and enzyme-linked
immunosorbent assays for cytokines, NF-�B, and cytochrome
c were performed. Levels of cytokines, inducible
nitric oxide synthase, caspases, Bcl-2, Bax, t-Bid, and
cytochrome c in the cell lysate and of NF-�B p65 in the
nucleus were determined by Western blotting. Microscopic
analysis, nuclear staining, DNA fragmentation
assay, fluorescence-activated cell sorting, colorimetric
assay for caspases, and fluorescent probe for measurement
of mitochondrial membrane potential were used to study the leishmanial lipid–induced apoptotic pathway
in SFMCs. Leishmanial lipid inhibited the release of
tumor necrosis factor �, interleukin-1�, and NO in the
culture, decreased their cytosolic protein levels, and
decreased NF-�B p65 levels in SFMCs, in a dosedependent
manner. It had the reverse effect on
interleukin-10 levels. Leishmanial lipid–induced apoptosis
involved the activation of caspase 3, caspase 9,
and Bax, the release of cytochrome c, the alteration of
mitochondrial membrane potential, and the downregulation
of Bcl-2. These results suggest that leishmanial
lipid has strong antiinflammatory and apoptosisinducing
effects on SFMCs from patients with RA, and
that apoptosis occurs via the mitochondrial pathway.
|
|
| Date |
2008
|
|
| Type |
Article
PeerReviewed |
|
| Format |
application/pdf
|
|
| Identifier |
http://www.eprints.iicb.res.in/288/1/ARTHRITIS_AND_RHEUMATISM%2C58(_3)%2C_696%2D706%2C2008[115].pdf
Majumdar, Kajal Nayan and Banerjee, Aditi and Ratha, Jagnyeswar and Mandal, Mriganka and Sarkar, Rathindra Nath and Das Saha, Krishna (2008) Leishmanial Lipid Suppresses Tumor Necrosis Factor �, Interleukin-1�, and Nitric Oxide Production by Adherent Synovial Fluid Mononuclear Cells in Rheumatoid Arthritis Patients and Induces Apoptosis Through the Mitochondrial-Mediated Pathway. Arthritis & Rheumatism, 58 (3). pp. 696-706. |
|
| Relation |
http://dx.doi.org/10.1002/art.23295
http://www.eprints.iicb.res.in/288/ |
|