Inflammation and apoptosis

Maier C. M., Ahem K., Cheng M. L., Lee J. E., Yenari M. A., and Steinberg G. K. (1998) Optimal depth and duration of mild hypothermia in a focal model of transient cerebral ischemia effects on neurologic outcome, infarct size, apoptosis, and inflammation. Stroke 29, 2171-2180. 

Maier et al., 1998 SD rats MCAo 2 h, with reperfusion 30, 33, and 37, during first 30 min, 1 h, or 2 h of ischemia Infarct size, neurologic function, apoptosis (TUNEL stain, morphology, DNA fragmentation), inflammation (MPO stain) 1 d and 3 d postreperfusion Reduced infarct size, improved neurologic function, reduced apoptosis and inflammation with 1 h or 2 h hypothermia... 

Hiller, S., Kohl, A., Fiorito, F., Herrmann, T., Wider, G., Tschopp, J., Grutter, M. G., and Wuthrich, K. (2003). NMR structure of the apoptosis- and inflammation-related NALPl pyrin domain. Structure (Camb) 11, 1199-1205. 

Turning off genes involved with proliferation, apoptosis, and inflammation... 

Caspases. Table 1 Diseases associated with inappropriate caspase activation. Contribution of apoptosis (A) and inflammation (I) are indicated... 

Inflammatory cytokines have been implicated in the pathophysiology of HF.9 Several proinflammatory (e.g., tumor necrosis factor-a [TNF-a], interleukin-1, interleukin-6, and interferon-y) and anti-inflammatory cytokines (e.g., interleukin-10) are overexpressed in the failing heart. The most is known about TNF-a, a pleiotrophic cytokine that acts as a negative inotrope, stimulates cardiac cell apoptosis, uncouples 3-adrenergic receptors from adenylyl cyclase, and is related to cardiac cachexia. The exact role of cytokines and inflammation in HF pathophysiology continues to be studied. 

Elgrabli, D. et al. (2008) Induction of apoptosis and absence of inflammation in rat lung after intratracheal instillation of multiwalled carbon nanotubes. Toxicology, 253 (1-3), 131-136. 

Holmin, S. and Mathiesen T. Intracerebral administration of interleukin-1 beta and induction of inflammation, apoptosis, and vasogenic edema. J. Neurosurg. 92, 108, 2000. 

The effect of MAPK activation on cellular processes that affect cell function and the resulting pharmacology has been delineated using modem techniques such as knock-out cells and animals [1,3,6]. Activation of MAPK in inflammatory cells such as T-cells, B-cells, macrophages and eosinophils leads to expression and/or activation of pro-inflammatory genes and mediators such as interleukin-1(3 (IL-1(3), TNFa, IL-6, chemokines [e.g., IL-8, macrophage inflammatory factor-1 a, (3 (MIP-la,[3)J, MMPs and toxic molecules such as free radicals and nitric oxide [1,3]. These pro-inflammatory mediators induce cellular proliferation, differentiation, survival, apoptosis and tissue degradation/destruction and help induce chronic inflammation. Inhibition of any one or more of the MAPK family... 

Trautmann A, Akdis M, Kleemann D, Altznauer F, Simon HU, Graeve T, NoU M, Brocker EB, Blaser K, Akdis CA T cell-mediated Fas-induced ker-atinocyte apoptosis plays a key pathogenetic role in eczematous dermatitis. J Clin Invest 2000 106 25-35. Schmidt-Weber CB, Blaser K Regulation and role of transforming growth factor-beta in immune tolerance induction and inflammation. 

The main differences between necrosis and apoptosis are in the triggers (accidental v. physiological), the process (energy-independent vs. dependent), and the outcomes (with vs. without inflammation). However, apoptosis and/or necrosis can be induced by the same causes in some cases (K16). Alteration of mitochondrial permeability is involved in both apoptosis and necrosis (K16). Both apoptosis and necrosis are found in conditions such as stroke and myocardial infraction (F5), and necrosis can occur secondary to apoptosis (T4). To preserve the usefulness of the two terms for denoting different modes of cell death while still recognizing possible overlap of the two processes (H7), some more descriptive terms have been proposed primary necrosis (oncosis, ischemic cell death) (Ml) and secondary necrosis (apoptotic necrosis, necrosis secondary to apoptosis) (K15). 

The expression of genes associated with excitotoxicity, oxidative stress, and inflammation-mediated apoptosis is controlled through cytokines and chemokines... 

Many skin disorders are associated with at least one of the characteristics of inflammation, oxidative stress, hyperproliferation, hypodifferentiation, infection, apoptosis, and autoimmune reactions. GTPs are uniquely positioned to antagonize these conditions with anti-inflammatory, antioxidant, antimicrobial, prodifferentiation, anti-apoptosis, and inhibition of autoantigen properties. Thus, many skin conditions, including autoimmune-induced lupus and psoriasis, wounds created by trauma or infections, damage induced by environmental factors such as UVB, and seborrheic dermatitis (dandruff), could be treated or managed by topical application of GTPs. 

---