Pseudolymphomatous folliculitis on the nose.

Pseudolymphomatous folliculitis (PLF), which sometimes mimicks cutaneous lymphoma, is a rare manifestation of cutaneous pseudolymphoma and cutaneous lymphoid hyperplasia. We describe a 57-year-old Japanese woman with PLF on the nose that resembled cutaneous lymphoma clinically. The biopsy specimen revealed dense lymphocytes, especially CD1a+ cells, infiltrated around the hair follicles. Without any additional treatment, her nodule rapidly decreased before we performed a second biopsy for analysis of the clonal gene rearrangement. Though PLF typically behaves as benign lymphohyperplasia, differentiation from cutaneous lymphoma is necessary.

Functional expression of heme oxygenase-1 in human differentiated epidermis and its regulation by cytokines.

Although heme oxygenase-1 (HO-1) is induced in keratinocytes after UV radiation, HO-1 expression during normal epidermal differentiation has not yet been reported. We showed by real-time PCR, western blotting, and ELISA that HO-1 mRNA and protein expression by cultured normal human keratinocytes was upregulated during epidermal differentiation induced by a high-calcium medium. Immunohistochemical staining and in situ hybridization showed the graduated expression of HO-1 in the upper epidermis, which was accompanied by suprabasal HO-1 mRNA expression, and the accumulation of bilirubin (BR) in the stratum corneum. We examined the activation of nuclear factor E2-related factor 2 (Nrf2), which is a pivotal transcription factor for HO-1 expression, by western blotting and by examining the mRNA expression of Nrf2 target genes, and excluded its role in HO-1 expression in epidermal differentiation. Next, we examined the regulation of HO-1 expression by inflammatory cytokines. IL-4 and IL-22 significantly reduced HO-1 mRNA and protein expression, whereas IL-1beta, IL-17A, and tumor necrosis factor-alpha (TNF-alpha) increased it. Finally, immunohistochemical studies on psoriatic lesional skin showed that HO-1 expression was downregulated in the parakeratotic epidermis, whereas it was retained in the orthokeratotic epidermis. These studies demonstrate that HO-1 is functionally expressed by keratinocytes in parallel with epidermal differentiation and that its expression is independently affected by several cytokines.

Prostaglandin D2 induces heme oxygenase-1 in human retinal pigment epithelial cells.

The retinal pigment epithelium (RPE) constitutes the blood-retinal barrier, whose function is impaired in various pathological conditions, including cerebral malaria, a lethal complication of Plasmodium falciparum infection. Prostaglandin (PG) D(2) is abundantly produced in the brain to regulate sleep responses. Moreover, PGD(2) is a potential factor derived from intra-erythrocyte falciparum parasites. Heme oxygenase-1 (HO-1) is important for iron homeostasis via catalysis of heme degradation to release iron, carbon monoxide and biliverdin/bilirubin, and may influence iron supply to the intra-erythrocyte falciparum parasites. Here, we showed that treatment of human RPE cell lines, ARPE-19 and D407, with PGD(2) significantly increased the expression levels of HO-1 mRNA, in a dose- and time-dependent manner. Transient expression assays showed that PGD(2) treatment increased the HO-1-gene promoter activity through the enhancer sequence, containing a Maf-recognition element. Thus, PGD(2) may contribute to the maintenance of heme homeostasis in the brain by inducing HO-1 expression.