title: Regulation of bitter taste responses by tumor necrosis factor.
abstract: Inflammatory cytokines are important regulators of metabolism and food intake. Over production of inflammatory cytokines during bacterial and viral infections leads to anorexia and reduced food intake. However, it remains unclear whether any inflammatory cytokines are involved in the regulation of taste reception, the sensory mechanism governing food intake. Previously, we showed that tumor necrosis factor (TNF), a potent proinflammatory cytokine, is preferentially expressed in a subset of taste bud cells. The level of TNF in taste cells can be further induced by inflammatory stimuli. To investigate whether TNF plays a role in regulating taste responses, in this study, we performed taste behavioral tests and gustatory nerve recordings in TNF knockout mice. Behavioral tests showed that TNF-deficient mice are significantly less sensitive to the bitter compound quinine than wild-type mice, while their responses to sweet, umami, salty, and sour compounds are comparable to those of wild-type controls. Furthermore, nerve recording experiments showed that the chorda tympani nerve in TNF knockout mice is much less responsive to bitter compounds than that in wild-type mice. Chorda tympani nerve responses to sweet, umami, salty, and sour compounds are similar between TNF knockout and wild-type mice, consistent with the results from behavioral tests. We further showed that taste bud cells express the two known TNF receptors TNFR1 and TNFR2 and, therefore, are potential targets of TNF. Together, our results suggest that TNF signaling preferentially modulates bitter taste responses. This mechanism may contribute to taste dysfunction, particularly taste distortion, associated with infections and some chronic inflammatory diseases.
authors.affiliation: Monell Chemical Senses Center, 3500 Market St., Philadelphia, PA 19104, USA. Electronic address: pfeng@monell.org.
authors.forename: Pu
authors.initials: P
authors.lastname: Feng
authors.affiliation: Monell Chemical Senses Center, 3500 Market St., Philadelphia, PA 19104, USA. Electronic address: mjotaki@monell.org.
authors.forename: Masafumi
authors.initials: M
authors.lastname: Jyotaki
authors.affiliation: Monell Chemical Senses Center, 3500 Market St., Philadelphia, PA 19104, USA. Electronic address: agnes.t.kim@gmail.com.
authors.forename: Agnes
authors.initials: A
authors.lastname: Kim
authors.affiliation: Monell Chemical Senses Center, 3500 Market St., Philadelphia, PA 19104, USA. Electronic address: jchai@monell.org.
authors.forename: Jinghua
authors.initials: J
authors.lastname: Chai
authors.affiliation: Monell Chemical Senses Center, 3500 Market St., Philadelphia, PA 19104, USA. Electronic address: n.simon.uchs@gmail.com.
authors.forename: Nirvine
authors.initials: N
authors.lastname: Simon
authors.affiliation: Monell Chemical Senses Center, 3500 Market St., Philadelphia, PA 19104, USA. Electronic address: mzhou@monell.org.
authors.forename: Minliang
authors.initials: M
authors.lastname: Zhou
authors.affiliation: Monell Chemical Senses Center, 3500 Market St., Philadelphia, PA 19104, USA. Electronic address: bachmanov@monell.org.
authors.forename: Alexander A
authors.initials: AA
authors.lastname: Bachmanov
authors.affiliation: Monell Chemical Senses Center, 3500 Market St., Philadelphia, PA 19104, USA. Electronic address: lhuang@monell.org.
authors.forename: Liquan
authors.initials: L
authors.lastname: Huang
authors.affiliation: Monell Chemical Senses Center, 3500 Market St., Philadelphia, PA 19104, USA. Electronic address: hwang@monell.org.
authors.forename: Hong
authors.initials: H
authors.lastname: Wang
mesh_terms: D000818:Animals; D001522:Behavior, Animal / Q000502:physiology; D002814:Chorda Tympani Nerve / Q000502:physiology; D019343:Citric Acid; D005260:Female; D007291:Inosine Monophosphate; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D011803:Quinine; D012439:Saccharin; D012965:Sodium Chloride; D012970:Sodium Glutamate; D013649:Taste / Q000502:physiology*; D013650:Taste Buds / Q000166:cytology / Q000378:metabolism; D055697:Taste Perception / Q000502:physiology*; D014409:Tumor Necrosis Factor-alpha / Q000235:genetics / Q000378:metabolism / Q000502:physiology*
chemical_list: D014409:Tumor Necrosis Factor-alpha; D007291:Inosine Monophosphate; D019343:Citric Acid; D012965:Sodium Chloride; D011803:Quinine; D012439:Saccharin; D012970:Sodium Glutamate
keywords: Cytokine; Inflammation; TNF; Taste buds; Taste-related behavior