linoleic-acid and Dermatitis

Peroxisome proliferator-activated receptor α (PPARα) is one of the three isoforms of PPARs, which are ligand-activated nuclear transcription factors. PPARα is highly expressed in liver and its agonists are widely used to treat hyperlipidemia. Epidermal keratinocytes express all three isoforms (α, β/δ, and γ) of PPARs and PPARα is particularly important for regulating the epidermal barrier and inflammation. Agonistic ligation of PPARα protects the epidermal barrier function and inhibits the inflammatory response in dermatitis. In this review, we summarize recent topics on the role of PPARα in skin biology and discuss the potential use of topical PPARα agonists for treating atopic dermatitis and other eczemas.

Topics: Administration, Topical; Animals; Anti-Inflammatory Agents; Dermatitis; Fenofibrate; Filaggrin Proteins; Humans; Hyperlipidemias; Keratinocytes; Linoleic Acid; Liver; PPAR alpha; Skin

The pathogenesis of acne is complex, with strong evidence supporting the involvement of sebaceous hyperplasia, follicular hyperkeratinisation, bacterial hypercolonisation, as well as immune reactions and inflammation. High sebum concentrations and follicular hyperkeratinisation lead to a change of the follicular milieu with consecutive proliferation of bacteria, chiefly Propionibacterium acnes. This leads to further increased production of the pro-inflammatory cytokines interleukin-1alpha and tumour necrosis factor alpha by T cells and keratinocytes, leading to proliferation of both cell types. Follicular keratinocytes fail to differentiate by apoptosis and produce hypergranulosis similar to the impermeable skin outer layer, resulting in the formation of microcomedones. Further inflammatory responses lead to the development of increasing degrees of severity in inflammatory forms of acne. Retinoids aid the differentiation and reduce the hyperproliferation of keratinocytes, and can inhibit the migration of leucocytes. Combination therapy using retinoids plus benzoyl peroxide or antibacterials can treat existing acne lesions faster than the individual agents alone and can also prevent the development of new lesions. The new retinoids (e.g. adapalene) have not only the typical potent comedolytic activity but also anti-inflammatory effects. When added to antibacterial therapy, topical retinoids demonstrate faster and significantly greater reduction of inflammatory acne lesions and comedones than antibacterials alone.

Topics: Acne Vulgaris; Administration, Oral; Administration, Topical; Androgens; Anti-Bacterial Agents; Benzoyl Peroxide; Dermatitis; Drug Therapy, Combination; Epithelial Cells; Gram-Positive Bacterial Infections; Humans; Linoleic Acid; Propionibacterium acnes; Retinoids; Sebaceous Glands; Sebum

Linoleic acid (C18: 2n-6) is a free fatty acid considered as essential in man; this is mainly based on the fact that man is incapable of its synthesis and that its deficiency accounts for a defined clinical picture. Linoleic acid (LA) is an essential component of cellular membranes and plays, therefore, an important role in cells; moreover, it plays a functional part on account of its precursory position of eicosanoids. For these reasons, the skin is a preferential target in case of LA deficiency, which alters the barrier function of the skin as well as the immunoregulation of the epidermic homeostasis. Man's requirement of LA has been estimated 4% of the total energy supply, i.e. 7-10 g daily. Deficiency of LA may arise from various factors: insufficient supply; metabolic anomalies (mostly due to advanced age and hepatopathies which may particularly alter the metabolic process of desaturation). Symptoms due to LA deficiency are xerosis and erythematosquamous dermatitis. The clinical picture being non-specific may be confused with other vitamin deficiencies, all the more because of metabolic interactions between these vitamins and various trace elements. Thus--in order to make the diagnosis--plasmatic fatty acid fractioning by means of gaseous phase chromatography is indicated in case of therapy-resistant eczematous dermatitis associated with malnutrition. These findings may be confirmed by measuring either the ratio of eicosatrienoic acid vs. arachidonic acid or the ratio of LA vs. arachidonic acid (in case of a disturbed metabolism of fatty acids). The treatment consists of regular oral, parenteral or topical application of essential fatty acids. Topical administration is especially indicated, because these patients, although often suffering from impaired intestinal absorption, reveal a tenfold percutaneous absorption rate of fatty acids.

Topics: Aged; Alcoholism; Dermatitis; Humans; Linoleic Acid; Linoleic Acids; Male

Skin colonization of Staphylococcus spp. critically affects the severity of dermatitis in humans and animals. We examined different types of fatty acid salts for their antibacterial activity against Staphylococcus spp. when used in ultrapure soft water (UPSW). We also evaluated their therapeutic effect on a spontaneous canine model of dermatitis.. UPSW, in which Ca(++) and Mg(++) were replaced with Na(+) , was generated using a water softener with cation-exchange resin. Staphylococcus aureus (Staph. aureus), Staphylococcus intermedius (Staph. intermedius), and Staphylococcus pseudintermedius (Staph. pseudintermedius) were incubated with various fatty acid salts in distilled water (DW) or UPSW and the number of bacteria was counted. Among the fatty acids, oleic acid salt and linoleic acid (LA) salt reduced the number of these bacteria. Also, UPSW enhanced the antibacterial effect of LA on Staph. spp. In spontaneously developed itchy dermatitis in companion dogs, shampoo treatment with liquid soap containing 10% LA in UPSW improved skin conditions.. LA salt showed antibacterial activity against Staph. spp. Treatment with soap containing LA with UPSW reduced clinical conditions in dogs with dermatitis.. Because colonization of Staph. spp. on the skin exacerbates dermatitis, the use of LA-containing soap in UPSW may reduce unpleasant clinical symptoms of the skin.

Topics: Animals; Anti-Bacterial Agents; Dermatitis; Dog Diseases; Dogs; Linoleic Acid; Oleic Acid; Skin; Soaps; Staphylococcal Infections; Staphylococcus; Water

The effects of oral ingestion of oleic (OLA) and linoleic (LNA) acids on wound healing in rats were investigated. LNA increased the influx of inflammatory cells, the concentration of hydrogen peroxide (H(2)O(2)) and cytokine-induced neutrophil chemoattractant-2αβ (CINC-2αβ), and the activation of the transcription factor activator protein-1 (AP-1) in the wound at 1  hour post wounding. LNA decreased the number of inflammatory cells and IL-1, IL-6, and macrophage inflammatory protein-3 (MIP-3) concentrations, as well as NF-κB activation in the wound at 24  hours post wounding. LNA accelerated wound closure over a period of 7 days. OLA increased TNF-α concentration and NF-κB activation at 1  hour post wounding. A reduction of IL-1, IL-6, and MIP-3α concentrations, as well as NF-κB activation, was observed 24  hours post wounding in the OLA group. These data suggest that OLA and LNA accelerate the inflammatory phase of wound healing, but that they achieve this through different mechanisms.

Topics: Administration, Oral; Animals; Chemokine CCL20; Dermatitis; Interleukin-1beta; Interleukin-6; Linoleic Acid; Male; Neutrophils; NF-kappa B; Oleic Acid; Rats; Rats, Wistar; RNA, Messenger; Skin; Transcription Factor AP-1; Tumor Necrosis Factor-alpha; Wound Healing

Ulcerative dermatitis (UD) is a common cause of morbidity and euthanasia in mice with a C57BL/6 (B6) background. The purposes of the current study were to determine whether UD lesions could be reliably produced in B6 mice lacking stearoyl-CoA desaturase 1 (SCD1(-/-) mice), to ascertain whether the UD lesions in SCD1(-/-) mice were similar to those found in other B6 mice, and to characterize the cell invasion phenotype of Staphlococcus xylosus cultured from the lesions. S. xylosus isolates from the environment and human skin were used as controls. SCD1(-/-) (n = 8 per group) and nontransgenic B6 control mice (n = 22 mice pooled from 3 groups that received different concentrations of conjugated linoleic acid) were fed standard rodent chow or a semipurified diet (NIH AIN76A) for 4 wk. Samples from other B6 mice with UD (field cases; n = 7) also were submitted for histology and culture. All of the SCD1(-/-) mice developed UD lesions by 4 wk on NIH AIN76A. None of SCD1(-/-) fed standard rodent chow and none of the wildtype B6 mice fed NIH AIN76A developed UD. Supplementation with conjugated linoleic acid did not affect ulcerogenesis. UD lesions in SCD1(-/-) mice and field cases were grossly and histologically similar. S. xylosus was isolated from SCD1(-/-) mice with UD (71%) and field cases of UD (43%). These isolates were the most cell-invasive, followed by the environmental isolate, and finally the human skin isolate. Our results provide a basis for further pathologic and clinical study of UD.

Topics: Animal Feed; Animals; Dermatitis; Female; Humans; Linoleic Acid; Mice; Mice, Inbred C57BL; Mice, Knockout; Rodent Diseases; Staphylococcus; Statistics, Nonparametric; Stearoyl-CoA Desaturase

(+/-)-13-Hydroxy-10-oxo-trans-11-octadecenoic acid (13-HOA) is one of the lipoxygenase metabolites of linoleic acid (LA) from corn germ. Recently, we reported that this metabolite suppressed the expression of lipopolysaccharide-induced proinflammatory genes in murine macrophages by disrupting mitogen-activated protein kinases and Akt pathways. In this study, we investigated the inhibitory effects of 13-HOA on 12-O-tetradecanoylphorbol-13-acetate (TPA)-induced inflammation in ears and skin, as well as tumor promotion in female ICR mice. Pretreatment with 13-HOA (1600 nmol) inhibited ear edema formation by 95% (P < 0.05) in an inflammation test and reduced tumor incidence and the number of tumors per mouse by 40 and 64% (P < 0.05 each), respectively, in a two-stage skin carcinogenesis model. Histological examinations revealed that it decreased epidermal thickness, the number of infiltrated leukocytes and cell proliferation index. Furthermore, 13-HOA (8-40 muM) suppressed TPA-induced anchorage-independent growth of JB6 mouse epidermal cells by 70-100%, whereas LA was virtually inactive. 13-HOA (40 muM) inhibited TPA-induced activator protein-1 transactivation but not extracellular signal-regulated kinase1/2 activation. Interestingly, 13-HOA (40 muM and 1600 nmol in JB6 cells and mouse skin, respectively) induced expression of programmed cell death 4 (Pdcd4), a novel tumor suppressor protein. To our knowledge, this is the first report of a food factor that is able to induce Pdcd4 expression. Collectively, our results indicate that 13-HOA may be a novel anti-inflammatory and antitumor chemopreventive agent with a unique mode of action.

Topics: Animals; Anti-Inflammatory Agents, Non-Steroidal; Anticarcinogenic Agents; Apoptosis Regulatory Proteins; Cell Transformation, Neoplastic; Dermatitis; Extracellular Signal-Regulated MAP Kinases; Fatty Acids, Unsaturated; Female; Linoleic Acid; Lipopolysaccharides; Mice; Mice, Inbred ICR; RNA-Binding Proteins; Skin; Skin Neoplasms; Tetradecanoylphorbol Acetate; Transcription Factor AP-1; Tumor Suppressor Proteins

Topics: Chromatography; Citrates; Dermatitis; Dietary Fats; Erythrocytes; Fatty Acids; Fatty Acids, Essential; Growth; Guinea Pigs; Ketoglutaric Acids; Linoleic Acid; Lipid Metabolism; Research

Topics: Animals; Dermatitis; Guinea Pigs; Linoleic Acid; Oleic Acid; Oleic Acids; Pharmacology; Radiation Injuries; Radiation Injuries, Experimental; Radiation-Protective Agents; Radiodermatitis; Research; Terpenes

Topics: Administration, Cutaneous; alpha-Linolenic Acid; Dermatitis; Fatty Acids; Fatty Acids, Unsaturated; Humans; Linoleic Acid