The Ras/Raf/extracellular signal-regulated kinase (ERK) signaling pathway plays a crucial role in almost all cell functions and therefore requires exquisite control of its spatiotemporal activity. Depending on the cell type and stimulus, ERK activity will mediate different antiproliferative events, such as apoptosis, autophagy and senescence in vitro and in vivo. ERK activity can promote either intrinsic or extrinsic apoptotic pathways by induction of mitochondrial cytochrome c release or caspase-8 activation, permanent cell cycle arrest or autophagic vacuolization. These unusual effects require sustained ERK activity in specific subcellular compartments and could depend on the presence of reactive oxygen species. We will summarize the mechanisms involved in Ras/Raf/ERK antiproliferative functions.

https://febs.onlinelibrary.wiley.com/doi/epdf/10.1111/j.1742-4658.2009.07366.x

ERK and cell death: Mechanisms of ERK‐induced cell death – apoptosis, autophagy and senescence

Compare your culture to one of the cultures discussed in this unit. On a sheet of paper, list the cultures you are comparing and make one column titled “similarities,” and a second column titled “differences.” Now, list as many similarities and differences between the two as you can think of. Are there more similarities or differences between the two cultures you selected? Have you ever met anyone from this culture? How can you use this information to build greater respect between cultures?

Similarities and Differences

Nitric oxide (NO), generated by the inducible isoform of nitric oxide synthase (iNOS), has been described to have beneficial microbicidal, antiviral, antiparasital, immunomodulatory, and antitumoral effects. However, aberrant iNOS induction at the wrong place or at the wrong time has detrimental consequences and seems to be involved in the pathophysiology of several human diseases. iNOS is primarily regulated at the expression level by transcriptional and post-transcriptional mechanisms. iNOS expression can be induced in many cell types with suitable agents such as bacterial lipopolysaccharides (LPS), cytokines, and other compounds. Pathways resulting in the induction of iNOS expression may vary in different cells or different species. Activation of the transcription factors NF-kappaB and STAT-1alpha, and thereby activation of the iNOS promoter, seems to be an essential step for iNOS induction in most cells. However, at least in the human system, also post-transcriptional mechanism are critically involved in the regulation of iNOS expression. The induction of iNOS can be inhibited by a wide variety of immunomodulatory compounds acting at the transcriptional levels and/or post-transcriptionally.

Regulation of the Expression of Inducible Nitric Oxide Synthase

Summary
Despite acne being an almost universal condition in younger people, relatively little is known about its epidemiology. We sought to review what is known about the distribution and causes of acne by conducting a systematic review of relevant epidemiological studies. We searched Medline and Embase to the end of November 2011. The role of Propionibacterium acnes in pathogenesis is unclear: antibiotics have a direct antimicrobial as well as an anti-inflammatory effect. Moderate-to-severe acne affects around 20% of young people and severity correlates with pubertal maturity. Acne may be presenting at a younger age because of earlier puberty. It is unclear if ethnicity is truly associated with acne. Black individuals are more prone to postinflammatory hyperpigmentation and specific subtypes such as ‘pomade acne’. Acne persists into the 20s and 30s in around 64% and 43% of individuals, respectively. The heritability of acne is almost 80% in first-degree relatives. Acne occurs earlier and is more severe in those with a positive family history. Suicidal ideation is more common in those with severe compared with mild acne. In the U.S.A., the cost of acne is over 3 billion dollars per year in terms of treatment and loss of productivity. A systematic review in 2005 found no clear evidence of dietary components increasing acne risk. One small randomized controlled trial showed that low glycaemic index (GI) diets can lower acne severity. A possible association between dairy food intake and acne requires closer scrutiny. Natural sunlight or poor hygiene are not associated. The association between smoking and acne is probably due to confounding. Validated core outcomes in future studies will help in combining future evidence.

https://onlinelibrary.wiley.com/doi/epdf/10.1111/bjd.12149

Epidemiology of acne vulgaris

Recent progress in phospholipase A₂ research: from cells to animals to humans.

Oatmeal has been used for centuries as a soothing agent to relieve itch and irritation associated with various xerotic dermatoses; however few studies have sought to identify the active phytochemical(s) in oat that mediate this anti-inflammatory activity. Avenanthramides are phenolic compounds present in oats at approximately 300 parts per million (ppm) and have been reported to exhibit anti-oxidant activity in various cell-types. In the current study we investigated whether these compounds exert anti-inflammatory activity in the skin. We found that avenanthramides at concentrations as low as 1 parts per billion inhibited the degradation of inhibitor of nuclear factor kappa B-α (IκB-α) in keratinocytes which correlated with decreased phosphorylation of p65 subunit of nuclear factor kappa B (NF-κB). Furthermore, cells treated with avenanthramides showed a significant inhibition of tumor necrosis factor-α (TNF-α) induced NF-κB luciferase activity and subsequent reduction of interleukin-8 (IL-8) release. Additionally, topical application of 1–3 ppm avenanthramides mitigated inflammation in murine models of contact hypersensitivity and neurogenic inflammation and reduced pruritogen-induced scratching in a murine itch model. Taken together these results demonstrate that avenanthramides are potent anti-inflammatory agents that appear to mediate the anti-irritant effects of oats.

Avenanthramides, polyphenols from oats, exhibit anti-inflammatory and anti-itch activity.

Hsp27 Regulates Pro-Inflammatory Mediator Release in Keratinocytes by Modulating NF-κB Signaling

The 60-kDa heat shock protein (HSP60), an endogenous ligand for the toll-like 4 receptor, is generated in response to inflammation, tissue injury, and/or stress and stimulates macrophages to produc...

https://www.physiology.org/doi/pdf/10.1152/ajpcell.00609.2001

Induction of cyclooxygenase-2 by heat shock protein 60 in macrophages and endothelial cells.

Excessive manganese exposure is toxic, but a comprehensive biochemical picture of this assault is poorly understood. Whether oxidative stress or reduced energy metabolism under manganese exposure causes toxicity is still a debate. To address this, we chose Δmnt P Escherichia coli, a highly manganese-sensitive strain, in this study. Combining microarray, proteomics, and biochemical analyses, we show that the chronic manganese exposure rewires diverse regulatory and metabolic pathways. Manganese stress affects protein and other macromolecular stability, and envelope biogenesis. Most importantly, manganese exposure disrupts both iron-sulfur cluster and heme-enzyme biogenesis by depleting cellular iron level. Therefore, the compromised function of the iron-dependent enzymes in the tricarboxylic acid cycle, and electron transport chain impede ATP synthesis, leading to severe energy deficiency. Manganese stress also evokes reactive oxygen species, inducing oxidative stress. However, suppressing oxidative stress does not improve oxidative phosphorylation and cell growth. On the contrary, iron supplementation resumed cell growth stimulating oxidative phosphorylation. Therefore, we hypothesize that affected energy metabolism is the primal cause of manganese toxicity.

/pdf/affected-energy-metabolism-under-manganese-stress-governs-4yttax50bt.pdf

Affected energy metabolism under manganese stress governs cellular toxicity.

The etiology of acne is a complex process, and acne is one of the most common skin disorders affecting millions of people. The pathogenesis of acne is closely associated with the bacterium, Propionibacterium acnes which was previously known as Corynebacterium parvum. Both viable and non-viable P. acnes/C. parvum have been shown to induce an immunostimulatory effect in vivo, suggesting that even dead bacteria continue to activate an inflammatory response. Acne treatments with lasers or devices, induce a bactericidal effect through heat generation which may not address the immunogenic activity of P. acnes and the resulting acne inflammation. Therefore, we sought to determine whether killed P. acnes is capable of inducing an inflammatory response and therefore could be a contributing factor in acne. Direct heat treatment of P. acnes cultures with temperatures ranging from 50 degrees C to 80 degrees C reduced P. acnes viability. Both viable and heat-killed P. acnes activated the p38 MAP kinase and its downstream substrate Hsp27. Stimulating keratinocytes with normal and heat-inactivated P. acnes resulted in an induction of proinflammatory nitric oxide and IL-8 production. Thus killed P. acnes is capable of inducing inflammation in skin suggesting that therapies that have both bactericidal and anti-inflammatory effects may result in a more effective treatment of patients with acne than treatments that are bactericidal alone.

Runa Sur

Papers

Avenanthramides, polyphenols from oats, exhibit anti-inflammatory and anti-itch activity.

Hsp27 Regulates Pro-Inflammatory Mediator Release in Keratinocytes by Modulating NF-κB Signaling

Induction of cyclooxygenase-2 by heat shock protein 60 in macrophages and endothelial cells.

Affected energy metabolism under manganese stress governs cellular toxicity.

Heat‐killed Propionibacterium acnes is capable of inducing inflammatory responses in skin