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Background Plants are hotbeds for parasites such as arthropod herbivores, which acquire nutrients and energy from their hosts in order to grow and reproduce. Hence plants are selected to evolve resistance, which in turn selects for herbivores that can cope with this resistance. To preserve their fitness when attacked by herbivores, plants can employ complex strategies that include reallocation of resources and the production of defensive metabolites and structures. Plant defences can be either prefabricated or be produced only upon attack. Those that are ready-made are referred to as constitutive defences. Some constitutive defences are operational at any time while others require activation. Defences produced only when herbivores are present are referred to as induced defences. These can be established via de novo biosynthesis of defensive substances or via modifications of prefabricated substances and consequently these are active only when needed. Inducibility of defence may serve to save energy and to prevent self-intoxication but also implies that there is a delay in these defences becoming operational. Induced defences can be characterized by alterations in plant morphology and molecular chemistry and are associated with a decrease in herbivore performance. These alterations are set in motion by signals generated by herbivores. Finally, a subset of induced metabolites are released into the air as volatiles and function as a beacon for foraging natural enemies searching for prey, and this is referred to as induced indirect defence. Scope The objective of this review is to evaluate (1) which strategies plants have evolved to cope with herbivores and (2) which traits herbivores have evolved that enable them to counter these defences. The primary focus is on the induction and suppression of plant defences and the review outlines how the palette of traits that determine induction/suppression of, and resistance/susceptibility of herbivores to, plant defences can give rise to exploitative competition and facilitation within ecological communities "inhabiting" a plant. Conclusions Herbivores have evolved diverse strategies, which are not mutually exclusive, to decrease the negative effects of plant defences in order to maximize the conversion of plant material into offspring. Numerous adaptations have been found in herbivores, enabling them to dismantle or bypass defensive barriers, to avoid tissues with relatively high levels of defensive chemicals or to metabolize these chemicals once ingested. In addition, some herbivores interfere with the onset or completion of induced plant defences, resulting in the plant's resistance being partly or fully suppressed. The ability to suppress induced plant defences appears to occur across plant parasites from different kingdoms, including herbivorous arthropods, and there is remarkable diversity in suppression mechanisms. Suppression may strongly affect the structure of the food web, because the ability to suppress the activation of defences of a communal host may facilitate competitors, whereas the ability of a herbivore to cope with activated plant defences will not. Further characterization of the mechanisms and traits that give rise to suppression of plant defences will enable us to determine their role in shaping direct and indirect interactions in food webs and the extent to which these determine the coexistence and persistence of species. [ABSTRACT FROM AUTHOR]

Background Fumaric acid esters ( FAEs) are widely used in Europe for the treatment of psoriasis because of their clinical efficacy and favourable safety profile. However, the mechanisms of action by which FAEs improve psoriasis remain largely unknown. Objectives To identify pathways and mechanisms affected by FAE treatment and to compare these with pathways affected by treatment with the antitumour necrosis factor (anti- TNF)-α biologic etanercept. Methods In a prospective cohort study, 50 patients with plaque psoriasis were treated with FAEs for 20 weeks. Nine patients were randomly selected for gene expression profiling of plaque biopsies from week 0 and week 12. The groups consisted of FAE responders [> Psoriasis Area and Severity Index ( PASI)-75 improvement] and nonresponders (< PASI-50 improvement). Changes in gene expression profiles were analysed using Ingenuity Pathway Analysis ( IPA) and the outcome was compared with gene expression affected by etanercept. Results Response to FAE treatment was associated with a ≥ 2-fold change ( P < 0·05) in the expression of 458 genes. In FAE responders the role of interleukin-17A in the psoriasis pathway was most significantly activated. Glutathione and Nrf2 pathway molecules were specifically induced by FAE treatment and not by etanercept treatment, representing an FAE-specific effect in psoriatic skin. In addition, FAE treatment specifically induced the transcription factors PTTG1, NR3C1, GATA3 and NFκ BIZ in responding patients. Conclusions FAE treatment induces glutathione and Nrf2 pathway genes in lesional skin of patients with psoriasis. In responders, FAEs specifically regulate the transcription factors PTTG1, NR3C1, GATA3 and NFκ BIZ, which are important in normal cutaneous development, and the T-helper (Th)2 and Th17 pathways, respectively. [ABSTRACT FROM AUTHOR]

Background Ustekinumab is a fully human anti-p40 monoclonal antibody which neutralizes interleukin (IL)-12 and IL-23, thereby interfering with T-helper (Th)1/Th17 pathways and keratinocyte activation, and is highly effective in the treatment of psoriasis. During ustekinumab treatment, some of our patients noticed reduced koebnerization of noninvolved skin and less new plaque formation. Objectives To determine whether ustekinumab improves psoriasis-related gene expression and tape-strip responses in noninvolved skin. Methods Before and 4 weeks after ustekinumab treatment, noninvolved skin was tape-stripped. After 5 h, biopsies were taken from untouched and tape-stripped skin. The mRNA expression of psoriasis-related markers such as NGF, GATA3 and IL-22RA1, and several antimicrobial peptides (AMP) was quantified. Leucocyte counts and a broad range of inflammatory serum proteins were analysed to gain insight into the systemic alterations. Results Four weeks following a single ustekinumab injection, NGF showed a significant decrease, whereas GATA3 and IL-22RA1 expression increased, indicative of reduced responsiveness to epidermal triggering. This was accompanied by an increase of the inflammation-related serum proteins GPNMB, MST1 and TRADD. The baseline and tape-strip-induced mRNA expression of the AMP human β-defensin-2 (hBD-2), S100A7 and LL-37 remained unaltered. Clinically, after 4 weeks, eight out of 11 patients showed a 50% psoriasis area and severity index (PASI) improvement, which was accompanied by a significant reduction in serum hBD-2 levels. No changes were noted in total leucocytes, C-reactive protein and erythrocyte sedimentation rate. Conclusions These findings indicate that ustekinumab reduces psoriasis-related gene expression in noninvolved psoriatic skin, making it more resistant to exogenous triggering, without disturbing its antimicrobial response. In parallel, ustekinumab modulates important circulating inflammation-related proteins. [ABSTRACT FROM AUTHOR]

The mode of action of narrowband ultraviolet B (NB-UVB) therapy in clearing psoriasis is incompletely understood, and in vivo studies at the molecular level in patients undergoing NB-UVB therapy are limited. We previously demonstrated increased expression and activity of double-stranded RNA (dsRNA) receptors in psoriasis lesions, and suggested that this enhanced innate signalling contributed to the maintenance of psoriatic inflammation. We investigated whether NB-UVB affects dsRNA receptor expression and function in vivo as well as in vitro. Skin samples of patients with psoriasis undergoing NB-UVB treatment were analysed for epidermal messenger RNA (mRNA) expression of the various dsRNA receptors by microarray and quantitative reverse transcription-polymerase chain reaction. Primary human keratinocytes were irradiated with NB-UVB and stimulated with interferon (IFN)-α or IFN-γ, critical cytokines in psoriasis. The dsRNA analogue polyriboinosinic-polyribocytidylic acid was used to assess the functional responsiveness of the cells to dsRNA. NB-UVB therapy of patients with psoriasis resulted in a significantly reduced mRNA expression of the activating dsRNA receptors MDA5 ( IFIH1) and RIG-I ( DDX58). On the other hand, expression of LGP2 ( DHX58), toll-like receptor 3 ( TLR3) and PKR ( EIF2AK2) was not affected. In vitro, NB-UVB irradiation completely blocked the upregulation of four of the dsRNA receptors in primary human keratinocytes stimulated with IFN-α or IFN-γ, resulting in an attenuated inflammatory response to dsRNA. Our results show that NB-UVB irradiation inhibits the local innate inflammatory response to dsRNA, and suggest a novel mechanism of action of NB-UVB phototherapy in psoriasis. [ABSTRACT FROM AUTHOR]

We developed a polymerase chain reaction (PCR) method, based on strain-to-strain variation of DNA repeats in the herpes simplex virus type 2 (HSV-2) genes US1 and US12, to genotype HSV-2 strains and determine the incidence and risk factors associated with HSV-2 superinfection in patients with recurrent genital herpes (RGH). Forty-seven (92%) of 51 unrelated HSV-2 isolates could be distinguished. Genotyping of sequential HSV-2 isolates showed a different genotype in all of the 11 human immunodeficiency virus type 1 (HIV-1)-seropositive patients with RGH, compared with 1 of the 8 HIV-1-seronegative patients with RGH. The PCR approach developed distinguishes unrelated HSV-2 strains efficiently and indicated a high incidence of genotype variance between sequential HSV-2 isolates of HIV-1-seropositive patients with RGH. Copyright © 2006 Infectious Diseases Society of America [ABSTRACT FROM AUTHOR]