Cytokines and chemokines

A number of adipokines are linked to inflammation and immunity (Fig. 1). This includes both leptin and adiponectin, and also a number of other key inflammatory proteins, particularly cytokines and chemokines [1]. The cytokines and chemokines encompass interleukin-1(3 (EL-1 (3), IL-6, DL-10, TNFa, monocyte chemoattractant protein-1 (MCP-1), and macrophage migration inhibitory factor (MIF). Other major inflammation-related adipokines include nerve growth factor (NGF), and acute phase proteins such as serum amyloid A and haptoglobin. In addition, adipocytes secrete plasminogen activator inhibitor-1 (PAI-1), which is an important thrombotic factor as well as an acute phase protein. 

Inflammatory disorders are due to hyperactivity of leukocytes and overexpression of their associated integrins, cytokines, and chemokines, which leads to various disorders including arthritis, bowel diseases and other chronic inflammations. 

In the late phase response, activated airway cells release inflammatory cytokines and chemokines, recruiting inflammatory cells into the lungs. The late phase response occurs 4 to 6 hours after the initial allergen challenge and results in a less intense bronchoconstriction as well as increased airway hyperresponsiveness and airway inflammation.6... 

Neutrophils are the most abundant leukocytes in humans, comprising about two thirds of peripheral blood leukocytes. Upon tissue injury, they rapidly infiltrate injury sites and play an important role in innate immune responses. In addition, they also contribute to the development of adaptive immune responses by producing an array of cytokines and chemokines. Tissue infiltration of neutrophils is initiated by signals generated by the interaction between chemoattractants produced at sites of injury and their corresponding cell surface receptors. Classical chemoattractants, such as C5a, N-formyl-methionyl-leucyl-... 

Szekanecz Z, Halloran MM, Volin MV, et al. Temporal expression of inflammatory cytokines and chemokines in rat adjuvant-induced arthritis. Arthritis Rheum 2000 43(6) 1266-1277. 

Thornton S, Duwel LE, Boivin GP, Ma Y, Hirsch R. Association of the course of collagen-induced arthritis with distinct patterns of cytokine and chemokine messenger RNA expression. Arthritis Rheum 1999 42(6) 1109-1118. 

Yara S, Kawakami K, Kudeken N, et al. FTS reduces bleomycin-induced cytokine and chemokine production and inhibits pulmonary fibrosis in mice. Clin Exp Immunol 2001 124(l) 77-85. 

It is clear that the type 2 cytokines IL-4, IL-9 and IL-13 play an obligatory role in host resistance to nematode infection whereas type 1 responses promote host susceptibility. Therefore, given that susceptibility to nematode infection is not due to a lack of responsiveness perse, but rather the development of an inappropriate response, it is important to understand the factors that influence the induction and expansion of Th subset responses and so control infection outcome. Studies in nematode models and other systems have addressed these questions and identified the importance of host genetic factors, the nature of the antigen and the antigen presenting cell, co-stimulatory molecules on these cells, and the cytokine and chemokine environment immediately following induction of the response. 

The family of heterotrimeric G proteins is involved in transmembrane signaling in the nervous system, with certain exceptions. The exceptions are instances of synaptic transmission mediated via receptors that contain intrinsic enzymatic activity, such as tyrosine kinase or guanylyl cyclase, or via receptors that form ion channels (see Ch. 10). Heterotrimeric G proteins were first identified, named and characterized by Alfred Gilman, Martin Rodbell and others close to 20 years ago. They consist of three distinct subunits, a, (3 and y. These proteins couple the activation of diverse types of plasmalemma receptor to a variety of intracellular processes. In fact, most types of neurotransmitter and peptide hormone receptor, as well as many cytokine and chemokine receptors, fall into a superfamily of structurally related molecules, termed G-protein-coupled receptors. These receptors are named for the role of G proteins in mediating the varied biological effects of the receptors (see Ch. 10). Consequently, numerous effector proteins are influenced by these heterotrimeric G proteins ion channels adenylyl cyclase phosphodiesterase (PDE) phosphoinositide-specific phospholipase C (PI-PLC), which catalyzes the hydrolysis of phosphatidylinositol 4,5-bisphosphate (PIP2) and phospholipase A2 (PLA2), which catalyzes the hydrolysis of membrane phospholipids to yield arachidonic acid. In addition, these G proteins have been implicated in... 

Wang, J., Asensio, V. C. and Campbell, I. L. Cytokines and chemokines as mediators of protection and injury in the central nervous system assessed in transgenic mice. Curr. Top. Microbiol. Immunol. 265 23-48, 2002. 

P Amyloid protein aggregation, leading to formation of plaques / Hyperphosphorylation of tau protein, leading to intracellular NFT development and collapse of microtubules / Inflammatory processes—levels of multiple cytokines and chemokines are elevated in AD brains / Neurovasculature dysfunction / Oxidative stress / Mitochondrial dysfunction... 

These authors identified novel serine kinases activated by cytokines and chemokines in T cells using PAP-1, and verified MAP kinase dependent IL-16 secretion in T-cell receptor-activated T cells. 

Several opiate receptors have been identified on cells of the nervous systems of animals and humans, with mu (p), kappa (k), and gamma (y) subtypes being predominant. These classical opiate receptors are G- protein coupled 7-transmembrane molecules.27 Opiates predominantly affect immune responses directly by ligation of p, k, and y opiate receptors, as well as non-classical opiate-like receptors, on immune cells and indirectly by binding to receptors on CNS cells. Studies conducted in vitro with opiate-treated immune cells demonstrated receptor-mediated reduced phagocytosis, chemotaxis and cytokine and chemokine production. These effects are linked to modulation of host resistance to bacterial, protozoan, viral and fungal infections using animal models, cell lines and primary cells. 

Kimber, I. et al., Cytokines and chemokines in the initiation and regulation of epidermal Langerhans cell mobilization. Br. J. Dermatol., 142,401, 2000. 

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