Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: EC:3.2.1.23 (beta-galactosidase)
 14,648 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Injury to the epidermis and other stratified epithelia triggers a repair response involving the rapid induction of several genes, including keratin 6 (K6). The signaling pathways and mechanisms presiding over this induction in keratinocytes at the wound edge remain to be defined. We reported previously that of the multiple genes encoding K6 isoforms in human, K6a is dominant in skin epithelia (Takahashi, K., Paladini, R., Coulombe, P. A. (1995) J. Biol. Chem. 270, 18581-18592). Using bacterial LacZ as a reporter gene in transgenic mice, we show that the proximal 5.2 kilobases of 5'-upstream sequence from the K6a gene fails to direct sustained expression in any adult tissue, including those where K6 is constitutively expressed (e.g. hair follicle, nail, oral mucosa, tongue, esophagus, forestomach). In contrast, the proximal 960 base pairs of 5'-upstream sequence suffice to mediate an induction of beta-galactosidase expression in a near-correct spatial and temporal fashion after injury to epidermis and other stratified epithelia. Transgene expression also occurs following topical application of phorbol esters, all-trans-retinoic acid, or 2-4-dinitro-1-fluorobenzene, all known to induce K6 expression in skin. Our data show that critical regulatory sequences for this inducibility are located between -960 and -550 bp in the 5'-upstream sequence of K6a and that their activity is influenced by enhancer element(s) located between -2500 and -5200 base pairs. These findings have important implications for the control of gene expression after injury to stratified epithelia.
 ...
PMID:Defining a region of the human keratin 6a gene that confers inducible expression in stratified epithelia of transgenic mice. 911 62

Lymphotoxin-beta is a newly recognized member of the tumor necrosis factor ligand family. Recent studies have suggested a role for this cytokine in delayed-type hypersensitivity responses. To determine whether lymphotoxin-beta contributes to the development of contact sensitivity, we utilized an inhibitor protein that can effectively block binding of lymphotoxin-beta to its receptor. An adenoviral vector was created that encodes for a lymphotoxin-beta inhibitor protein consisting of the extracellular domain of the lymphotoxin-beta receptor fused to IgG heavy chain. Intravenous injection of the recombinant virus into BALB/c mice yielded plasma levels of inhibitor protein > 500 micrograms that persisted for 1 week. Mice treated in this manner were compared with control animals injected with adenovirus encoding beta-galactosidase, with respect to their ability to mount contact sensitivity responses to epicutaneously applied dinitro-fluorobenzene. Mice transduced with the lymphotoxin-beta inhibitor prior to the induction of contact sensitivity showed significantly suppressed ear swelling responses. By contrast, mice treated with the lymphotoxin-beta inhibitor prior to the elicitation of contact sensitivity showed no change in ear swelling responses in comparison to controls. These findings indicate that lymphotoxin-beta plays an important role in the afferent phase of the contact sensitivity response.
 ...
PMID:Adenovirus-mediated blockade of lymphotoxin-beta inhibits the induction of contact sensitivity in mice. 929 89