Corynebacterium species are commonly found in the conjunctiva of healthy adults and are recognized as non-pathogenic bacteria. In recent years, however, Corynebacterium species have been reported to be potentially pathogenic in various tissues. We investigated Corynebacterium species on the ocular surface and reviewed various species of Corynebacterium in terms of their antimicrobial susceptibility and the underlying molecular resistance mechanisms. We identified a risk for Corynebacterium-related ocular infections in patients with poor immunity, such as patients with diabetes or long-term users of topical steroids, and in those with corneal epithelial damage due to trauma, contact lens wear, lagophthalmos, and trichiasis. The predominant strain in the conjunctiva was C. macginleyi, and the species associated with keratitis and conjunctivitis were C. macginleyi, C. propinquum, C. mastitidis, C. pseudodiphtheriticum, C. accolens, C. striatum, C. xerosis, and C. bovis. Overall, Corynebacterium species present on the ocular surface were resistant to quinolones, whereas those in the nasal cavity were more susceptible. The prevalence of fluoroquinolone-resistant Corynebacterium has not changed in the past 10 years; however, Corynebacterium species remain susceptible to third-generation cephems. In conclusion, the use of third-generation cephems should be a reasonable and pragmatic approach for treatment of ocular infections caused by Corynebacterium species.

Membrane type 1 matrix metalloproteinase (MT1‐MMP) with a transmembrane domain is a new member of the MMP gene family and is expressed on the cell surfaces of many carcinoma cells to activate the zymogen of MMP‐2 (gelatinase A). We have previously reported that MT1‐MMP is released into culture media in a complex form with tissue inhibitor of metalloproteinases 2 (TIMP‐2) from a human breast carcinoma cell line, MDA‐MB‐231, treated with concanavalin A (Con A). In the present study, we further studied the release mechanism of MT1‐MMP. Immunoblot analysis indicated that the amounts of MT1‐MMP in culture media increase with the time of exposure and the concentration of Con A, and those in cell lysates conversely decrease in a similar way. Time‐ and dose‐dependent release of MT1‐MMP into the media was confirmed by a sandwich enzyme immunoassay specific to MT1‐MMP. The molecular weight of the immunoreactive MT1‐MMP in the media was M_r 56,000, which was 4,000‐M_r smaller than that in the cell lysates. Northern blot analysis demonstrated that the mRNA expression level of MT1‐MMP is about 3‐fold enhanced after a 24 h‐exposure to Con A and this is maintained up to 72‐h exposure. The release of MT1‐MMP from the Con A‐treated cells was inhibited by metalloproteinase inhibitors such as EDTA and o‐phenanthroline, but not by MMP inhibitors including TIMP‐1, TIMP‐2 and BB94 or other proteinase inhibitors of serine, cysteine and aspartic proteinases. During the Con A treatment of the cells, cell viability decreased time‐ and dose‐dependently and dead cells reacted positively in the TdT‐mediated dUTP Nick‐End Labeling (TUNEL) method. Con A‐treated MDA cells showed apoptotic morphology when stained with Hoechst dye and hematoxylin and eosin. DNA ladder formation was detected by electrophoresis of the DNA from Con A‐treated MDA cells. These results suggest that MT1‐MMP release from Con A‐treated cells is due to shedding mediated by metalloproteinase(s) other than MMPs, and is associated with apoptosis.

Chronic dermatitis, such as contact dermatitis (CD) or atopic dermatitis (AD), is a long‐standing inflammatory skin disease with cutaneous damage such as erosion, ulceration, and lichenification due to itch‐induced scratching. The resultant lesion can be considered to be a kind of wound. The tissue inhibitor metalloproteases‐2 (TIMP‐2) accelerates wound healing by enhancing the proliferation and migration of epidermal keratinocytes and dermal fibroblasts; it is also a physiologic inhibitor of matrix metalloproteinases. The aim of this study was to test the effect of TIMP‐2 on chronic dermatitis. NC/Kuj mice were sensitized with Dermatophagoides farinae (Df) extract. Eczema was induced by repeated applications of this mite allergen to the skin of 20 sensitized mice that were maintained under specific pathogen‐free conditions. One group of 10 mice was then treated with topical TIMP‐2 solution (0.1 ml, 0.5%) for 28 days, and the other with vehicle alone and the effects of TIMP‐2 were evaluated macro‐ and microscopically. The effect on skin barrier function was estimated by measuring transepidermal water loss (TEWL). Scoring of gross skin findings showed that TIMP‐2 significantly reduced the severity of eczema (P <0.05) on days 12–28. Histological examination revealed that TIMP‐2 treated mice manifested lower degrees of hyperkeratosis, acanthosis, and spongiosis in the epidermis and fewer inflammatory cells in the dermis than vehicle‐treated mice. There were significant reductions in the epidermal thickness and dermal inflammatory cells in the TIMP‐2 treated animals (P <0.01); their TEWL was significantly decreased on day 28 (P <0.05). Our results suggest that NC/Kuj mice with Df extract‐induced chronic eczema may be a useful model for investigating chronic dermatitis, and that TIMP‐2 may be a good agent for treating chronic dermatitis as well as chronic ulcers.

An amendment to this paper has been published and can be accessed via a link at the top of the paper.