263
the development of anti-inflammatory compounds. The natural or synthetic structural analogs of their kinase substrate have been shown to inhibit inflammatory
response in vivo. Since most of these inhibitors are small molecules, they hold
potential pharmacological significance. Enzymes like phosphodiesterase, aldose
reductase, and cyclin-dependent kinase and pro-resolving mediators like endogenous autacoids like lipoxins and their receptors are recently getting attention as
anti-inflammatory therapeutic targets. Similarly, NFκB, involved in the biosynthetic
pathway of proinflammatory cytokines, is also considered as a target of antiinflammatory drug development. In addition, adhesion molecules which are
involved in leukocyte extravasation, could serve as attractive anti-inflammatory
drug targets. The search for more selective drugs against many inflammation-based
diseases such as rheumatoid arthritis, inflammatory bowel disease, allergies, multiple sclerosis, asthma, atherosclerosis, etc., has suggested that ICAMs could function as better therapeutic agents. Integrins are the principal proteins involved in
immune-cell extravasations. Inflammatory reactions can be reduced via interfering
with the signaling events preventing extravasation of leukocytes via integrins. Toll
like receptor 5 (TLK5) is recognised as a potential antiinflammatory target.
Microgliosis is an important feature of Alzheimer’s disease (AD) etiology. Amyloid
β peptide is hypothesized to act as a stimulus for microglia followed by nonreceptor
tyrosine kinases and secretion of proinflammatory cytokines. Therefore, the signaling pathways mediating microglial activation can be considered for pharmacological exploitation in search of anti-inflammatory therapy for AD. The significance of
vascular endothelial cells (VECs) revealed their role in leukocyte recruitment, cytokine production, and angiogenesis. Therefore, drugs targeting VECs may yield
great therapeutic benefit against many (chronic) inflammatory disorders. The potential role of miRNAs in the regulation of basic inflammation and in the pathogenesis
of many autoimmune and inflammatory diseases has been unraveled. miRNAs,
miR-126, miR-132, miR-146, miR-155, and miR-221, are strongly implicated with
proinflammatory responses (Wang et al. 2010). Strategies can be adopted to control
inflammation at the genetic and epigenetic level as the next-generation therapeutics.
Gene therapy via synthetic oligonucleotides against micro-RNAs and proinflammatory genes can be envisaged as future therapeutic perspective against autoimmune
and hypersensitive diseases where genetic factors serve as a significant contributing
factor.
10.9 Conclusions
Undesired and persistent inflammatory response is a major hallmark of immune
disorders and cause of transplant rejections. Therapeutic amelioration of many
autoimmune and hypersensitive diseases still extends limited efficacy. Antiinflammatory molecules with potential ability to reduce hyperimmune response
underlying such manifestations offer a promising therapeutic strategy. Antagonists
targeting cytokines, eicosanoids, histamines and the components of complements
have shown to ameliorate inflammatory and immune responses and thus, these
10 Anti-inflammatory Molecules: Immune System Mediators
the development of anti-inflammatory compounds. The natural or synthetic structural analogs of their kinase substrate have been shown to inhibit inflammatory
response in vivo. Since most of these inhibitors are small molecules, they hold
potential pharmacological significance. Enzymes like phosphodiesterase, aldose
reductase, and cyclin-dependent kinase and pro-resolving mediators like endogenous autacoids like lipoxins and their receptors are recently getting attention as
anti-inflammatory therapeutic targets. Similarly, NFκB, involved in the biosynthetic
pathway of proinflammatory cytokines, is also considered as a target of antiinflammatory drug development. In addition, adhesion molecules which are
involved in leukocyte extravasation, could serve as attractive anti-inflammatory
drug targets. The search for more selective drugs against many inflammation-based
diseases such as rheumatoid arthritis, inflammatory bowel disease, allergies, multiple sclerosis, asthma, atherosclerosis, etc., has suggested that ICAMs could function as better therapeutic agents. Integrins are the principal proteins involved in
immune-cell extravasations. Inflammatory reactions can be reduced via interfering
with the signaling events preventing extravasation of leukocytes via integrins. Toll
like receptor 5 (TLK5) is recognised as a potential antiinflammatory target.
Microgliosis is an important feature of Alzheimer’s disease (AD) etiology. Amyloid
β peptide is hypothesized to act as a stimulus for microglia followed by nonreceptor
tyrosine kinases and secretion of proinflammatory cytokines. Therefore, the signaling pathways mediating microglial activation can be considered for pharmacological exploitation in search of anti-inflammatory therapy for AD. The significance of
vascular endothelial cells (VECs) revealed their role in leukocyte recruitment, cytokine production, and angiogenesis. Therefore, drugs targeting VECs may yield
great therapeutic benefit against many (chronic) inflammatory disorders. The potential role of miRNAs in the regulation of basic inflammation and in the pathogenesis
of many autoimmune and inflammatory diseases has been unraveled. miRNAs,
miR-126, miR-132, miR-146, miR-155, and miR-221, are strongly implicated with
proinflammatory responses (Wang et al. 2010). Strategies can be adopted to control
inflammation at the genetic and epigenetic level as the next-generation therapeutics.
Gene therapy via synthetic oligonucleotides against micro-RNAs and proinflammatory genes can be envisaged as future therapeutic perspective against autoimmune
and hypersensitive diseases where genetic factors serve as a significant contributing
factor.
10.9 Conclusions
Undesired and persistent inflammatory response is a major hallmark of immune
disorders and cause of transplant rejections. Therapeutic amelioration of many
autoimmune and hypersensitive diseases still extends limited efficacy. Antiinflammatory molecules with potential ability to reduce hyperimmune response
underlying such manifestations offer a promising therapeutic strategy. Antagonists
targeting cytokines, eicosanoids, histamines and the components of complements
have shown to ameliorate inflammatory and immune responses and thus, these
10 Anti-inflammatory Molecules: Immune System Mediators