Free IL-18 levels are specifically elevated in AOSD compared with other inflammatory diseases, suggesting that IL-18 represents a potential target for the treatment of AOSD.

The ability of thioredoxin f to form an electrostatic (non-covalent) complex, earlier found with fructose-1,6-bisphosphatase, was extended to include 27 previously unrecognized proteins functional in 11 processes of chloroplasts. The proteins were identified by combining thioredoxin f affinity chromatography with proteomic analysis using tandem mass spectrometry. The results provide evidence that an association with thioredoxin enables the interacting protein to achieve an optimal conformation, so as to facilitate: (i) the transfer of reducing equivalents from the ferredoxin/ferredoxin-thioredoxin reductase complex to a target protein; (ii) in some cases, to enable the channeling of metabolite substrates; (iii) to function as a subunit in the formation of multienzyme complexes.Abbreviations: FBPase -fructose-1,6-bisphosphatase; FTR -ferredoxin-thioredoxin reductase

Lee, Rees L., Raymond C. Rancourt, Greg del Val, Kami Pack, Churee Pardee, Frank J. Accurso, and Carl W. White. Thioredoxin and dihydrolipoic acid inhibit elastase activity in cystic fibrosis sputum.

Epidermal LC play a critical role in the initiation and regulation of skin immune and allergic responses. LC migration, including that stimulated by allergen, is dependent upon cytokine signals, provided by tumor necrosis factor-α (TNF-α) and interleukin (IL)-1β. We have examined the ability of two human recombinant proteins with immunomodulatory properties to influence LC migration : thioredoxin (Trx), a (12kDa) redox-active protein and lactoferrin (LF), a (79.5kDa) iron-binding protein, produced in E. coli and rice, respectively. LC migration in response to chemical contact allergen (oxazolone; Ox) or to murine TNF-α or IL-1β was assessed in BALB/c mice. Mice were treated by simple topical exposure to TRX or LF 2 h prior to treatment with the migratory stimuli. LC densities were assessed in epidermal sheets by staining for MHC class II or Langerin. Topical application of Trx inhibited Ox- and TNF-α-induced migration whereas LF prevented LC mobilisation stimulated by Ox and IL-1β only. Inhibition of LC migration by TRX was selective for IL-1β-dependent stimuli (Ox and TNF-α) whereas TNF-α-dependent migration (that provoked by Ox and IL-1β) was inhibited by LF. These data suggest that TRX modulates IL-1β production/signaling whereas LF inhibits the activity of TNF-α. The bioactivity of these molecules following topical exposure shows that these proteins can access the viable epidermis and may represent an opportunity for the development of novel anti-inflammatory reagents.

Epidermal LC play a critical role in the initiation of skin immune responses. LC migration is dependent upon cytokine signals, provided by tumour necrosis factor-α (TNF-α) and interleukin (IL)-1β. We have now examined the ability of human recombinant thioredoxin (hTrx), a redox-active protein, to influence LC migration. Wild type hTrx and various cysteine to alanine mutants were produced in E coli. LC migration in response to chemical contact allergen (oxazolone; Ox) or to intradermal (id) injection of recombinant murine TNF-α or IL-1β was assessed in BALB/c mice. LC migration was provoked in healthy human volunteers (n=10) by id injection of recombinant human TNF-α. Various forms of hTrx were administered by topical application 2h prior to the migratory stimuli. LC densities were assessed in epidermal sheets by immunofluorescent staining for MHC class II (mouse) or CD1a (human). Topical application of hTrx inhibited significantly Ox- and TNF-α-induced LC migration in BALB/c strain mice, but failed to impact on IL-1β-induced migration. Use of mutant forms of hTrx demonstrated that this ability was redox-independent. Application to the skin of wild type hTrx to human volunteers inhibited TNF-α-induced LC migration also. Inhibition of LC migration was selective for IL-1β-dependent stimuli (contact allergen and TNF-α). These data suggest that thioredoxin possesses novel immunomodulatory properties as a result of its ability to modulate IL-1β production and/or signalling.