No abstract

Immune cell Toll-like receptors (TLRs) recognize conserved microbial components, leading to immune and inflammatory responses. However, TLRs are also expressed in cancer cells, including melanoma cells, which express TLR2-4. TLR4 ligands have received attention as immunotherapies; therefore, we assessed the expression of TLR4 in human melanoma specimens (29 primary lesions and 28 metastatic lesions) representing different types of melanoma. A high percentage (≥ 90%) of melanoma lesions expressed TLR4, as judged by immunohistochemistry. Next, the role of TLR4 in cell proliferation and migration was assessed using the TLR4-positive (TLR4 + ) melanoma cell lines 501mel and 888mel, and TLR4-negative (TLR4 -) 928mel melanoma cells. Lipopolysaccharide (LPS), a TLR4 agonist, increased the proliferation of TLR4 + melanoma cells but not of TLR4 -928mel cells. The proliferation-inducing effect of LPS in 888mel cells was abolished by blockade of TLR4 signaling via treatment with short interfering RNA (siRNA) targeting TLR4 or myeloid differentiation primary response gene 88 (MyD88), a molecule downstream of TLR4. However, knockdown of TLR4 or MyD88 expression did not affect the LPS-induced proliferation of 501mel cells, suggesting that residual TLR4 signaling is sufficient to maintain cell proliferation. By contrast, LPS increased the migration of TLR4 + melanoma cells, and this effect was substantially inhibited by TLR4 or MyD88 knockdown. Furthermore, TLR4 knockdown decreased cell migration even in the absence of LPS, suggesting the presence of an endogenous TLR4 ligand(s) in melanoma cells. TLR4 signaling may contribute to melanoma progression, and caution should be exercised when using TLR4 ligands as adjuvant therapy for cancer.

Dear Editor, Bullous pemphigoid (BP) is an autoimmune disease that tends to occur in elderly individuals. Here, we report a case that developed BP after receiving the second dose of coronavirus disease 19 (COVID-19) vaccine. The patient, an 83-year-old Japanese woman with bipolar disorder, was treated for xerotic eczema in a clinic and her eczema was relieved with topical steroids. Three days after receiving the second dose of tozinameran, the BNT162b2 mRNA COVID-19 vaccine, F I G U R E 1 (a,b) Histopathological images (hematoxylin-eosin). (a) Subepidermal bulla (original magnification ×5) and (b) vacuolar degeneration at the epidermis−dermis junction with eosinophilic infiltration (×100). (c) Direct immunofluorescence showed the linear deposition of immunoglobulin G at the basement membrane zone. (d,e) Clinical images. (d) Diffuse erythema and erosion and (e) blisters

Notch down-regulation in regenerated epidermis contributes to enhanced expression of interleukin-36α and suppression of keratinocyte differentiation during wound healing