Related Experiment Video
Updated: Jul 10, 2026
07:45
Acute Myocardial Infarction in Rats
Published on: February 16, 2011
[p38 MAP Kinase inhibitor].
Masataka Nishikawa1, Akira Myoui, Tetsuya Tomita
1Department of Orthopaedic Surgery, Toyonaka Municipal Hospital.
Summary
FR167653, a p38 MAP Kinase inhibitor, effectively prevented and treated arthritis in rats. It reduced inflammation, joint damage, and osteoclast formation, indicating p38 MAP Kinase as a therapeutic target for rheumatoid arthritis.
Area of Science:
- Immunology
- Pharmacology
- Rheumatology
Context:
- Rheumatoid arthritis (RA) is a chronic inflammatory disease characterized by joint destruction.
- p38 MAP Kinase plays a significant role in inflammatory processes and cytokine production.
- FR167653 is a known inhibitor of p38 MAP Kinase, impacting tumor necrosis factor-alpha (TNF-alpha) and interleukin-1beta (IL-1beta) production.
Purpose:
- To investigate the therapeutic potential of FR167653 in a rat model of collagen-induced arthritis (CIA).
- To evaluate the effects of FR167653 on arthritis onset, progression, and joint damage.
- To explore the impact of FR167653 on inflammatory markers and osteoclast formation.
Summary:
- FR167653 administration, both prophylactically and therapeutically, significantly reduced hind paw swelling in CIA rats.
- Treatment with FR167653 led to lower radiographic and histologic scores, and decreased osteoclast numbers compared to untreated CIA rats.
- FR167653 decreased serum and ankle levels of TNF-alpha and IL-1beta, and inhibited in vitro osteoclast differentiation induced by sRANKL and TNF-alpha.
Impact:
- FR167653 demonstrated efficacy in preventing arthritis onset and suppressing joint destruction progression in CIA rats.
- These findings highlight p38 MAP Kinase as a potential therapeutic target for managing rheumatoid arthritis.
- The study provides evidence for the anti-inflammatory and anti-arthritic effects of p38 MAP Kinase inhibition.
Related Concept Videos
01:07MAPK Signaling Cascades
Mitogen-activated protein kinase, or MAPK pathway, activates three sequential kinases to regulate cellular responses such as proliferation, differentiation, survival, and apoptosis. The canonical MAPK pathway starts with a mitogen or growth factor binding to an RTK. The activated RTKs stimulate Ras, which recruits Raf or MAP3 Kinase (MAPKKK), the first kinase of the MAPK signaling cascade. Raf further phosphorylates and activates MEK or MAP2 Kinases (MAPKK), which in turn phosphorylates MAP...
01:22PI3K/mTOR/AKT Signaling Pathway
The mammalian target of rapamycin (mTOR) is a serine/threonine kinase that regulates growth, proliferation, and cell survival in response to hormones, growth factors, or nutrient availability. This kinase exists in two structurally and functionally distinct forms: mTOR complex 1 (mTORC1) and mTOR complex 2 (mTORC2). The first form (mTORC1) is composed of a rapamycin-sensitive Raptor and proline-rich Akt substrate, PRAS40. In contrast, mTORC2 consists of a rapamycin-insensitive companion...
01:19Interactions Between Signaling Pathways
Signaling cascades usually lack linearity. Multiple pathways interact and regulate one another, allowing cells to integrate and respond to diverse environmental stimuli.
Convergence and divergence, and cross-talk between signaling pathways
Two distinct signaling pathways can converge on a single functional unit, which may either be a single protein or a complex of proteins. The response is either functionally distinct or synergistic between the two pathways but different from the response...
Convergence and divergence, and cross-talk between signaling pathways
Two distinct signaling pathways can converge on a single functional unit, which may either be a single protein or a complex of proteins. The response is either functionally distinct or synergistic between the two pathways but different from the response...
01:20The JAK-STAT Signaling Pathway
Several cytokine receptors have tightly bound Janus kinase or JAK proteins attached at their cytosolic tail. Small signaling molecules such as cytokines, growth hormones, or prolactins bind to the cytokine receptors and initiate their dimerization. The dimerization brings the cytosolic JAKs together that trans-phosphorylate and activates each other. The activated JAKs now phosphorylate cytosolic tails of the cytokine receptors, which serve as binding sites for adaptor proteins such as SH2...
01:42Microtubule Associated Proteins (MAPs)
Microtubule function and architecture are regulated by an array of specialized proteins called microtubule-associated proteins or MAPs. These proteins are widespread across different organisms and have conserved protein motifs, like the multi-TOG domain for tubulin binding found in the CLASP family of MAPs. Some MAPs are lineage-specific based on their conserved domains. Their functions depend upon the cytoskeletal architecture and cell type they are located within. In-plant cells, a specific...
02:34Inhibition of Cdk Activity
The orderly progression of the cell cycle depends on the activation of Cdk protein by binding to its cyclin partner. However, the cell cycle must be restricted when undergoing abnormal changes. Most cancers correlate to the deregulated cell cycle, and since Cdks are a central component of the cell cycle, Cdk inhibitors are extensively studied to develop anticancer agents. For instance, cyclin D associates with several Cdks, such as Cdk 4/6, to form an active complex. The cyclin D-Cdk4/6 complex...