Ribosomal inactivation damages 28S ribosomal RNA by interfering with its functioning during gene translation, leading to stress responses linked to a variety of inflammatory disease processes. Although the primary effect of ribosomal inactivation in cells is the functional inhibition of global protein synthesis, early responsive gene products including proinflammatory cytokines are exclusively induced by toxic stress in highly dividing tissues such as lymphoid tissue and epithelia. In the present study, ribosomal inactivation-related modulation of cytokine production was reviewed in leukocyte and epithelial pathogenesis models to characterize mechanistic evidence of ribosome-derived cytokine induction and its implications for potent therapeutic targets of mucosal and systemic inflammatory illness, particularly those triggered by organellar dysfunctions. 1. Introduction As the functional organelle for protein synthesis, ribosomes bound to the endoplasmic reticulum (ER) perform complex surveillance of various pathologic stresses [1–3]. Ribosomal alteration by endogenous and external insults can trigger a variety of pathogenic processes, including inflammatory responses [4–6]. Ribosomal inactivation can be induced by a large family of ribonucleolytic proteins that cleave 28s ribosomal RNA at single phosphodiester bonds within a universally conserved sequence known as the sarcin-ricin loop, which leads to the dysfunction of peptidyltransferase and subsequent global translational arrest [7, 8]. These ribosome-inactivating proteins (RIPs) are enzymes isolated mostly from plants and some of RIPs such as ricins and shiga toxins are potent cytotoxic biological weapons causing tissue injuries and inflammatory diseases [9, 10]. Similar ribosomal RNA injuries have been observed during nonprotein ribosome-inactivating stress triggered by physical and chemical insults such as ultraviolet (UV) irradiation, trichothecene mycotoxins (mostly cereal contaminants produced by molds such Fusarium species), palytoxin (an intense vasoconstrictor produced by marine species including dinoflagellate Ostreopsis ovata), and anisomycin (an antibiotic produced by Streptomyces griseolus), which also interfere with peptidyltransferase activity by directly or indirectly modifying 28s rRNA [11, 12]. The primary action of most ribosome-inactivating stress is the functional inhibition of global protein synthesis; therefore, highly dividing tissues such as lymphoid tissue and mucosal epithelium are the most susceptible targets of the stress [13–15]. Although acute high levels of toxic
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