Prostanoids, consisting of the prostaglandins (PGs) and the thromboxanes (TXs), are a group of lipid mediators formed in response to various stimuli. They include PGD₂, PGE₂, PGF_2α, PGI₂, and TXA₂. Given that aspirin-like nonsteroidal anti-inflammatory drugs exert their actions by suppressing prostanoid production, prostanoids have been implicated in processes inhibited by these drugs, including inflammation, fever, and pain. However, how prostanoids exert such a variety of actions had remained unclear. Prostanoids are released outside of the cells immediately after synthesis, and exert their actions by binding to receptors on the surface of target cells. We have identified a family of eight types or subtypes of G protein-coupled receptors that mediate prostanoid actions. They are the PGD receptor (DP), four subtypes of the PGE receptor (EP₁, EP₂, EP₃, and EP₄), the PGF receptor (FP), PGI receptor (IP), and TXA receptor (TP). Recently mice deficient in each of these prostanoid receptors were generated and subjected to various experimental models of disease. These studies have not only elucidated the molecular and cellular mechanisms of known prostanoid actions but also revealed previously unknown actions. In this article, we review several recent findings of the roles of prostanoid receptor signalling in inflammation, allergy, and immunity.

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A pterygium is a wing-shaped, fibrovascular conjunctival outgrowth, invading centripetally into the clear cornea, and its incidence is associated with sun exposure (ultraviolet radiation). We investigated whether epithelial-mesenchymal transition (EMT) is involved in the pathogenesis of pterygium. Histopathology showed aberrant fibrotic proliferation beneath the pterygium epithelium, with epithelial processes extending into the stroma. Transmission electron microscopy revealed the dissociation of epithelial cells, which were surrounded by activated fibroblast-like cells. Characteristic downregulation of E-cadherin and intranuclear accumulation of β-catenin and lymphoid-enhancer-factor -1 in pterygial epithelium were also observed by immunohistology. Interestingly, epithelial cells extending into the stroma were positive for both α-SMA/Vimentin and cytokeratin 14. Snail and Slug were immunopositive in the nuclei of pterygial epithelial cells, but not in normal corneal epithelial cells. These results suggested that EMT of basal epithelial cells may play a key role in the pathogenesis of pterygium.

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Although many cytokines are involved in the pathophysiology of spinal cord injury (SCI), the role of each cytokine remains elusive. Many lines of evidence have indicated that the excess inflammation elicited by pro-inflammatory cytokines exhibit neuronal and glial toxicity and that administration of several anti-inflammatory drugs can prevent this extensive secondary injury. Besides targeting secondary injury, modulating cytokine signaling is also an attractive therapeutic strategy as differentiational regulator for neural stem/progenitor cells. Here, we review the role of cytokine signaling which are both deleterious and beneficial in the pathophysiology for spinal cord injury, with an emphasis on the role of IL-6 signaling.

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A wide variety of neurons and glial cells are generated in the developing central nervous system (CNS). The precise regulation of cell-type determination and cell number is thought to be indispensable for the appropriate development and physiological functions of the CNS. Both extrinsic and intrinsic molecular mechanisms, which regulate timing and position in cytogenesis, enable the acquisition of diversity and the control of numbers in neurons and glial cells. The specification of neurons and glial cells in the embryonic spinal cord has been intensively studied. Distinct types of neurons and glial cells are generated along the dorsoventral axis of the embryonic spinal cord, which is regulated by extracellular molecules and transcriptional codes. However, the molecular mechanisms regulating cytogenesis of certain progenitor cells through extracellular molecules have been poorly elucidated. We have recently demonstrated that epidermal growth factor (EGF) signaling via Grb2 associated binder1 (Gab1) contributes to the proliferation of Olig2-positive progenitors that sequentially generate motoneuron and glial cells in the developing spinal cord, in a time and position-restricted manner. In this review, the molecular mechanisms of progenitor proliferation via EGF signaling will be discussed by focusing on the embryonic spinal cord.

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Phospholipase A₂ is a group of lipolytic enzymes that catalyze the hydrolysis of the sn-2 position of glycerophospholipids to yield fatty acids and lysophosphplipids. In mammals, PLA₂ enzymes have been divided into three major classes, including cytosolic PLA₂s (cPLA₂s), Ca²⁺-independent PLA₂s (iPLA₂s), and secreted PLA₂s (sPLA₂s). Whereas the important role of cPLA_2α, a prototypic cPLA₂, in arachidonate metabolism has been well established, the functions and relevant substrates of other PLA₂s, sPLA₂s in particular, have still remained elusive. Individual sPLA₂s show distinct tissue and cellular distributions and enzymatic properties, suggesting their distinct physiological roles. This review summarizes the latest information on the functional aspects of four sPLA₂s, namely sPLA₂-IB, IIA, V and X, which distinctly participate in dietary phospholipid digestion, anti-bacterial defense, airway pathology, atherosclerosis, and possibly skin homeostasis.

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An 83-year-old female with hip joint fracture developed severe dyspnea and was admitted to our hospital. On admission, her blood gas analysis indicated hypoxemia. Her chest radiograph showed a ground-grass pattern in bilateral lung fields and enlargement of right atrium. The level of neutrophil elastase activity was elevated. She was diagnosed as post embolism syndrome. A treatment with sodium sivelestat hydrate, a neutrophil elastase inhibitor, intravenously, was started at the second hospital day. The level of neutrophil elastase activity returned to normal after the treatment. Her respiratory condition was improved. We experienced that a case of post embolism syndrome was improved by treating with neutrophil elastase.

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